Intermediates and processes for preparing 4-substituted 2-5(H)-furanones as anti-inflammatory agents

ABSTRACT

Anti-inflammatory 4-substituted 2-furanones are made from intermediates having the formulas:  (* CHEMICAL STRUCTURE *) Formula 1   (* CHEMICAL STRUCTURE *) Formula 2   (* CHEMICAL STRUCTURE *)    (* CHEMICAL STRUCTURE *)

BACKGROUND OF THE INVENTION

1. Cross-Reference to Related Applications

This application is a divisional of application Ser. No. 07/792,833,filed Nov. 15, 1991 issued as U.S. Pat. No. 5,171,563, which is adivisional of application Ser. No. 07/690,444, filed Apr. 24, 1991 nowissued as U.S. Pat. No. 5,082,954, and which is a continuation-in-partof the following applications, all of which are assigned to the sameassignee as the present application, and all of which have at least oneinventor common with the present application: application Ser. No.07/493,895 filed on Mar. 15, 1990, now U.S. Pat. No. 5,081,147;application Ser. No. 07/510,368 filed on Apr. 17, 1990, now U.S. Pat.No. 5,037,811; application Ser. No. 07/192,808 filed on May 11, 1988,now abandoned which is itself a continuation-in-part of application Ser.No. 059,282 filed on Jun. 8, 1987, now abandoned; application Ser. No.07/510,367 field on Apr. 17, 1990now U.S. Pat. No. 5,043,457;application Ser. No. 07/427,268 filed on Oct. 25, 1989, now U.S. Pat.No. 5,059,611 which is itself a continuation-in-part of application Ser.No. 273,300 field on Nov. 18, 1989, now abandoned which is itself acontinuation-in-part of application Ser. No. 281,154 filed on Dec. 7,1988, now abandoned; application Ser. No. 07/426,243 filed on Oct. 25,1989, now U.S. Pat. No. 5,089,485 which is itself a continuation-in-partof application Ser. No. 273,294 filed on Nov. 18, 1988, now abandoned.

2. Field of the Invention

This is directed to novel 2-trialkylsily 4-substituted furan compoundswhich serve as intermediates for the synthesis of biologically activesubstituted 2-furanone compounds which are active as anti-inflammatoryagents. The present invention is also directed to the chemical processesin which the novel 2-trialkylsilyl 4-substituted furan compoundsintermediates are prepared, and to the chemical processes in which theanti-inflammatory substituted 2-furanone compounds are prepared from thenovel intermediate compounds.

3. Brief Description of the Prior Art

Manoalide is a compound isolated from a marine sponge [E. D. de Silva etal., Tetrahedron Letters 21:1611-1614 (1980)] which hasanti-inflammatory, immunosuppressive and analgesic properties. Manoalidethe structure of which is shown below, includes a5-hydroxy-2(5H)-furanone moiety, attached in the 4-position of thefuranone ring to the rest of the molecule. Certain analogs of manolide,such as seco-manoalide and dehydro-seco-manoalide also haveanti-inflammatory activity. For further description of the biologicalactivity of manoalide and some of its derivatives reference is made toU.S. Pat. Nos. 4,447,445, 4,786,651, 4,789,749 and to European PatentApplication No. 0,133,376 (published on Feb. 20, 1985). ##STR2##

Synthetic analogs of manoalide, particularly analogs having varioussubstituents on the furanone moiety of manoalide, are described inseveral applications for United States Letters Patent by the sameinventor as in the present application, the following of which have beenallowed and are expected to issue as United States Letters Patent:

Application Ser. No. 281,126 filed on Dec. 7, 1988.

Published European Patent Application No. 0,295,056 discloses4-substituted 5-hydroxy-2(5H)-furanones having antiinflammatory,immunosuppressive and anti-proliferative activity where the substituentsin the 4 position are a variety 1-hydroxyalkyl, 1-acyloxy-alkyl and1-carbamoyloxy-alkyl groups.

U.S. Pat. No. 4,855,320 discloses 5-arylalkyl-4-alkoxy-2(5H)-furanonesas anti-convulsive and anti-epileptic agents

Published European Patent Application No. 0,209,274 discloses4-alkyl-5-hydroxy-2(5H)-furanones as anti-inflammatory and anti-allergyagents.

Chemical Abstracts Volume 107 236559t (1987) discloses 4-acyloxy5-hydroxy-2(5H)-furanones.

In addition to the foregoing references which are primarily directed tobiologically active 2(5H)-furanone derivatives, the following patentsand publications pertain to the chemistry of furan compounds, asbackground to the present invention:

U.S. Pat. No. 4,935,530; Feringa, B.L. Recl. Trav. Chim. Pays-Bas.(1987), 106, 469; Wasserman, H.R.; Ives, J.L. Tetrahedron (1981), 37,1825; Matsumoto, M. in "Singlet oxygen" vol. II, edited by Frimer A.A.,CRC Press Inc., Boca Raton, Florida, 1985; Kuwajima, I.; Urabe, H.Tetrahedron Lett (1981), 22, 5191; Katsumura, S.; Hori, K.; Fujimara,S.; Isoe, S. Tetrahedron Lett. (1985), 26, 4625; Garst, M.E.; Tallman,E.A.; Bonfiglio, J.N.; Harcourt, D.; Ljungwe, E.B.; Tran, A. TetrahedronLett. (1986), 27, 4533.

SUMMARY OF THE INVENTION

The present invention covers compounds of the formula ##STR3## in whichR₁, R₂ and R₃ independently are n-alkyl of 1 to 6 carbons, or branchedchain alkyl of 1 to 6 carbons; x is H, OH, NH₂, I or Br; R₄ is H, alkylof 1-20 carbons, phenyl[C₁ -C₂₀ alkyl], naphthyl[C₁ -C₂₀ alkyl], CH₂ OH,CH₂ NH₂, CH₂ CH₂ OH, CH₂ --CHO, CH₂ --COOH or CH₂ --COOR₅, and R₅ isalkyl of 1 to 6 carbons, with the proviso that when x is hydrogen thenR₄ is selected from the group consisting of CH₂ OH, CH₂ NH₂, CH₂ CH₂ OH,CH₂ --CHO, or CH₂ --COOR₅.

The present invention also covers compounds of the formula ##STR4## inwhich R₁, R₂ and R₃ independently are n-alkyl of 1 to 6 carbons, orbranched chain alkyl of 1 to 6 carbons, and R₅ is alkyl of 1 to 6carbons.

Further, the present invention covers compounds of the formula ##STR5##in which R₁, R₂ and R₃ independently are n-alkyl of 1 to 6 carbons, orbranched chain alkyl of 1 to 6 carbons, and R₆ is phenyl, or alkyl of 1to 6 carbons.

Still further the present invention covers compounds of the formula##STR6## in which R₁, R₂ and R₃ independently are n-alkyl of 1 to 6carbons, or branched chain alkyl of 1 to 6 carbons.

In another aspect the present invention relates to the processes inwhich the above-defined compounds are made. In still another aspect thepresent invention relates to the chemical processes in which the novelcompounds of the invention, as generally represented by Formulas 1-4,are converted into the anti-inflammatory furanone compounds. These stepsare described in detail in the ensuing description, and generallyspeaking include one or more steps where the substituent in 4-positionof the furan nucleus (as shown in Formulas 1-4) is reacted With suitablereagents, and a step wherein an intermediate2-trialkylsilyl-4-substituted furan is subjected to oxydation by singletoxygen, to provide, generally speaking, a hydroxylated furanone Withreference to the compounds of the invention shown in Formula 1, singletoxydation of intermediates derived from that formula provide, inaccordance with the present invention, anti-inflammatory 4-substituted5-hydroxy-2(5H)-furanones.

General Embodiments Definitions

The terms "ester", "amine", "amide", "ether" and all other terms andterminology used here, (unless specifically defined in the presentdescription) refer to and cover any compounds falling within therespective term as that term is classically used in organic chemistry.

Unless specifically noted otherwise, preferred esters are derived fromthe saturated aliphatic alcohols or acids of ten or fewer carbon atomsor from the cyclic or saturated aliphatic cyclic alcohols and acids of 5to 10 carbon atoms. Particularly preferred aliphatic esters are thosederived from lower alkyl acids or alcohols. Also preferred are thephenyl or lower alkylphenyl esters.

The term "alkyl" as used in the present description and claims includesstraight chain alkyl groups, branched chain alkyl groups, cycloalkylgroups, alkyl substituted cycloalkyl groups, and cycloalkyl substitutedalkyl groups. Unless the number of carbons is otherwise specified,"lower alkyl" means the former broad definition of "alkyl" groups butwith the restriction that the group has 1 to 6 carbon atoms.

Unless specifically noted otherwise, the term "long chain alkyl" alsomeans the former broad definition of "alkyl" groups but with therestriction that the group has no less than 4 carbon atoms, and no morethan approximately 25 carbon atoms.

Unless specifically noted otherwise, preferred amides are the mono- anddi-substituted amides derived from the saturated aliphatic radicals often or fewer carbon atoms, or the cyclic or saturated aliphatic-cyclicradicals of 5 to 10 carbon atoms.

Some of the compounds of the invention, and some of theanti-inflammatory furanone compounds which are made from the compoundsof the invention, may contain a chiral center. Other compounds of theinvention, and some of the anti-inflammatory furanone compounds whichare made from the compounds of the invention, may contain more than onechiral center. Accordingly, these compounds may be prepared as mixturesof enantiomeric compounds (where the enatiomers may or may not bepresent in equal amounts) or as optically pure enantiomers When there ismore than one chiral center, the compounds may also be prepared asmixtures of diastereomers, or as pure diastereomers, and eachdiastereomer itself may be a mixture of enantiomers in 1:1, or other,ratios. Alternatively, each diastereomeric compound may be stericallyand optically pure. However, all of the above-noted forms, includingoptically pure enantiomers and mixtures thereof, as well as alldiastereomers, are within scope of the present invention.

Some of the compounds of the invention, and some of theanti-inflammatory furanone compounds which are made from the compoundsof the invention, may have cis and trans stereoisomers. The scope of theinvention includes both pure stereoisomers as well as mixtures thereof.

A pharmaceutically acceptable salt may be prepared from any of theanti-inflammatory furanone compounds made in accordance with thisinvention from the intermediate compounds of this invention, providedthe anti-inflammatory furanone has a functionality capable of formingsuch salt, for example an acid or an amine functionality. Apharmaceutically acceptable salt may be any salt which retains theactivity of the parent compound and does not impart any deleterious oruntoward effect on the subject to which it is administered and in thecontext in which it is administered.

Such a salt may be derived from any organic or inorganic acid or base.The salt may be a mono or polyvalent ion. Of particular interest wherethe acid function is concerned are the inorganic ions, sodium,potassium, calcium, and magnesium. Organic amine salts may be made withamines, particularly ammonium salts such as mono-, di- and trialkylamines or ethanol amines. Salts may also be formed with caffeine,tromethamine and similar molecules. Where there is a nitrogensufficiently basic as to be capable of forming acid addition salts, suchmay be formed with any inorganic or organic acids or alkylating agentsuch as methyl iodide. Preferred salts are those formed with inorganicacids such as hydrochloric acid, sulfuric acid or phosphoric acid. Anyof a number of simple organic acids such as mono-, di- or tri-acid mayalso be used.

The preferred compounds of the present invention with reference toFormula 1 and with respect to the R₁, R₂, and R₃ groups, are those whereR₁, R₂, and R₃ independently are normal alkyl of 1 to 6 carbons, orbranched chain alkyl of 1 to 6 carbons. More preferred are compounds ofFormula 1 where R₁, R₂, and R₃ are all methyl, or all ethyl, and alsocompounds where R₁ and R₂ are methyl and R₃ is tertiary butyl.

With respect to R₄ in Formula 1, the preferred compounds in accordancewith the invention are those where R₄ is H, or a long chain alkyl groupof 4 to 25 carbons, more preferably a long chain alkyl group having 9 to20 carbons. Alternatively and preferably R₄ is CH₂ OH, CH₂ NH₂, CH₂ CH₂OH, CH₂ --CHO, CH₂ --COOH or CH₂ --COOCH₃ or CH₂ --COOCH₂ CH₃.

With respect to the substituent x in Formula 1, the preferred compoundsare those where x is H, OH or NH₂, with the condition that when x is Hthen R₄ is not H nor alkyl.

The most preferred compounds of the invention corresponding to Formula1, are listed below:

    Compound 1 R.sub.1 ═R.sub.2 ═R.sub.3 ═CH.sub.3 CH.sub.2 --, X═OH and R.sub.4 ═H;

    Compound 2 R.sub.1 ═R.sub.2 ═R.sub.3 ═CH.sub.3 CH.sub.2 --, X═NH.sub.2 and R.sub.4 ═H;

    Compound 3 R.sub.1 ═R.sub.2 ═R.sub.3 ═CH.sub.3 CH.sub.2 --, X═OH and R.sub.4 ═CH.sub.3 (CH.sub.2).sub.11 --;

    Compound 4 R.sub.1 ═R.sub.2 ═R.sub.3 ═CH.sub.3 CH.sub.2 --, X═NH.sub.2 and R.sub.4 ═CH.sub.3 (CH.sub.2) .sub.11 --;

    Compound 5 R.sub.1 ═R.sub.2 ═R.sub.3 ═CH.sub.3 CH.sub.2 --, X═H and R.sub.4 ═CH.sub.2 CHO;

    Compound 6 R.sub.1 ═R.sub.2 ═R.sub.3 ═CH.sub.3 CH.sub.2 --, X═OH and R.sub.4 ═CH.sub.2 OH;

    Compound 7 R.sub.1 ═R.sub.2 ═R.sub.3 ═CH.sub.3 CH.sub.2 --, X═OH and R.sub.4 ═CH.sub.2 NH.sub.2 ;

    Compound 8 R.sub.1 ═R.sub.2 ═R.sub.3 ═CH.sub.3 CH.sub.2 --, X═NH.sub.2 and R.sub.4 ═CH.sub.2 NH.sub.2 ;

    Compound 8 R.sub.1 ═R.sub.2 ═R.sub.3 ═CH.sub.3 CH.sub.2 --, X═I and R.sub.4 ═H.

The preferred compounds of the present invention shown by Formula 2, arethose where the R₁, R₂, and R₃ groups are normal alkyl of 1 to 6carbons, or branched chain alkyl of 1 to 6 carbons. More preferred arecompounds of Formula 2 where R₁, R₂, and R₃ are all methyl, or allethyl, and also compounds where R₁ and R₂ are methyl and R₃ is tertiarybutyl.

With respect to R₅ in Formula 2 in the preferred compounds of theinvention R₅ is normal alkyl, most preferably methyl or ethyl. Methyl3-(2-triethylsilyl-4-furyl)propen-2-oate (Compound 10) and Octyl3-(2-triethylsilyl-4-furyl)propen-2-oate (Compound 11) and thecorresponding trimethylsilyl derivatives, are examples of the mostpreferred compounds in this regard.

Among the compounds of the invention shown by Formula 3A and 3B thoseare preferred where R₁, R₂, and R₃ groups are normal alkyl of 1 to 6carbons, or branched chain alkyl of 1 to 6 carbons. More preferred arecompounds of Formula 3 where R₁, R₂, and R₃ are all methyl, or allethyl, and also compounds where R₁ and R₂ are methyl and R₃ is tertiarybutyl. Compounds of this formula are further preferred where R₆ ismethyl and n is 1 or 2. The most preferred compounds in this regard are2-triethylsilyl-3-methyl-4-furaldehyde (Compound 12) and2-trimethylsilyl-5-methyl-4-furaldehyde (Compound 13),2-triethylsilyl-3,5-dimethyl-4-furaldehyde (Compound 14) and thecorresponding (and respective) trimethyl silyl or triethyl silylderivatives.

With respect to the compounds of the invention shown in Formula 4A andFormula 4B, those are preferred where the R₁, R₂, and R₃ groups arenormal alkyl of 1 to 6 carbons, or branched chain alkyl of 1 to 6carbons. More preferred are compounds of Formula 4A and 4B where R₁, R₂,and R₃ are all methyl, or all ethyl, and also compounds where R₁ and R₂are methyl and R₃ is tertiary butyl. The most preferred compound ofFormula 4A is 2-triethylsilyl-3-furaldehyde (Compound 15).

The compounds of the invention are useful as intermediates in thesynthesis of compounds which themselves are useful in pharmaceuticalcompositions to produce anti-inflammatory, immunosuppressant andanti-proliferative activity. The diseases, syndromes or conditions ofmammals (including humans) which can be treated with pharmaceuticalcompositions containing one or more compounds (or salts thereof) madefrom the intermediates of this invention include: inflammation,rheumatoid arthritis, osteoarthritis, rheumatic carditis, ocular anddermal inflammatory diseases, autoimmune diseases such as allergicdiseases, bronchial asthma and myasthenia gravis, unwanted immuneresponses and unwanted proliferation of cells, psoriasis, acne, atopicdiseases and allergic conjunctivitis.

The activity of the compounds prepared from the intermediates of thisinvention is demonstrated by inhibition of the enzyme phospholipase A2in vitro and by reduction of inflammation in the mouse earanti-inflammatory assay in vivo.

Activity of compounds prepared from the compounds of this invention mayalso be demonstrated by inhibition of phosphoinositide-specificphospholipase C. This activity has been reported for manoalide and mayindicate anti-inflammatory utility. Bennett et al, MolecularPharmacology 32:587-593 (1987).

Activity of the compounds prepared from the compounds of the inventionmay also be demonstrated by inhibition of ornithine decarboxylase, arate limiting enzyme in cellular growth, which indicates use in treatingpsoriasis and neoplasis.

The compounds prepared from the intermediates of this invention alsomodify calcium homeostasis. This activity is shown by effect onintracellular calcium levels in experiments using gastric glands, spleencells, epithelial cells, GH₃ cells, etc. Calcium is inhibited fromentering through the plasma membrane calcium channels and calciumrelease from intracellular stores is also blocked. Modification ofcalcium homeostasis is expected to have application in diseases of thenervous system involving modification of membrane lipids or transmitterrelease (Parkinson's, Alzheimer's), diseases of the cardiovascularsystem involving application of cardiac or vascular smooth musclecontractility and platelet aggregation (hypertension, cardiac infarctionand atherosclerosis), diseases of the gastrointestinal tract such asulcer disease, diarrhea, motility due to secretion of acid or C1⁻,diseases of the kidney involving renal handling of fluid andelectrolytes (metabolic acidosis, alkalosis), and disease of abnormalgrowth (neoplasia, psoriasis).

The biologically active compounds prepared from the compounds of thisinvention have activity which is similar to having anti-inflammatoryimmunosuppressive properties.

The biologically active compounds made from the intermediate compoundsof the invention are administered to mammals, including humans, in aneffective amount to produce the desired activity, preferably in anamount of about 0.05 to 100 mg per day per kilogram of body weight. Theamount of the compound depends upon the disease or condition beingtreated, the severity thereof, the route of administration and thenature of the host. The compounds may be administered topically, orally,parenterally or by other standard routes of administration.

The pharmaceutical compositions in which the biologically activecompounds, made from the intermediate compounds of this invention, areadministered, comprise the active compounds as well as pharmaceuticalcarriers suitable for the route of administration Standard methods forformulating pharmaceutical compositions of this type may be found inRemington's Pharmaceutical Sciences, Mack Publishing Company, Easton,PA.

For topical administration, the pharmaceutical composition may be in theform of a salve, cream, ointment, spray, powder or the like. Standardpharmaceutical carriers for such compositions may be used. Preferably,compositions for topical administration will contain 0.05-5% of theactive ingredient.

A typical cream formulation may contain the following:

    ______________________________________                                        Ingredient          Parts by Weight                                           ______________________________________                                        Water/glycol mixture                                                                              50-99                                                     (15% or more glycol)                                                          Fatty alcohol       1-20                                                      Non-ionic surfactant                                                                              0-10                                                      Mineral oil         0-10                                                      Typical pharmaceutical adjuvants                                                                  0-5                                                       Active ingredient   0.05-5                                                    ______________________________________                                    

A typical ointment formulation may contain the following:

    ______________________________________                                        Ingredients     Parts by Weight                                               ______________________________________                                        White petrolatum                                                                              40-94                                                         Mineral oil     5-20                                                          Glycol solvent  1-15                                                          Surfactant      0-10                                                          Stabilizer      0-10                                                          Active ingredient                                                                             0.05-5                                                        ______________________________________                                    

For oral administration, suitable pharmaceutical carriers includemannitol, lactose, starch, magnesium stearate, talcum, glucose andmagnesium carbonate. Oral compositions may be in the form of tablets,capsules, powders, solutions, suspensions, sustained releaseformulations, and the like.

A typical tablet or capsule may contain the following:

    ______________________________________                                        Ingredients      Percent w/w                                                  ______________________________________                                        Lactose, spray-dried                                                                           40-99                                                        Magnesium stearate                                                                             1-2                                                          Cornstarch       10-20                                                        Active ingredient                                                                              0.001-20                                                     ______________________________________                                    

Parenteral compositions are prepared in conventional suspension orsolution forms, as emulsions or as solid forms for reconstruction.Suitable carriers are water, saline, dextrose, Hank's solution, Ringer'ssolution, glycerol, and the like. Parenteral administration is usuallyby injection which may be subcutaneous, intramuscular or intravenous.

The active compounds prepared from the intermediate compounds of thisinvention, may be combined with other knownanti-inflammatory/immunosuppressive agents such as steroids ornon-steroidal anti-inflammatory agents (NSAID) in the pharmaceuticalcompositions and methods described herein.

The assay procedures by which useful biological activity of thecompounds can be demonstrated, are described below.

Calcium Channel (mobilization) Inhibition Assay

Polymorphonuclear leukocytes (PMNa), gastric glands, GH₃ cells, A431cells, spleen cells, human keratinocytes corneal cells, etc. were loadedwith the Ca²⁺ sensitive fluorescent dye, Fura-2. The appropriate celltype was chosen and the potency and efficacy of the anti-inflammatoryfuranones on calcium mobilization, calcium channel inhibition wasquantitated. The methods used for A431 cells listed below arerepresentative of those used for other cells.

A431 cells were detached using a 5-10 min trypsin-EDTA treatment whereasGH₃ cells were treated 2 to 5 min with a 1% pancreatin solution. Cellswere immediately washed twice in a 20mM HEPES buffer (pH 7.4) containing120mM NaCl, 6 mM KCl, 1 mM MgSO₄, 1 mg/ml glucose and 1 mg/ml pyruvateand 1.4mM calcium (medium A). Approximately 5×10⁶ cells were suspendedin medium A and incubated with 4uM fura-2-AM for 15 min at 37° C.

After washing the fura-2 loaded cells, the uptake of dye was checkedusing fluorescence microscopy and found to be evenly distributed in thecytosol of all cells. Fluorescence was continuously recorded with aPerkin-Elmer LS-5 spectrofluorometer. The excitation wavelength was setat 340nm and emission wavelength set at 500nm. The cell suspension wascontinually stirred, maintained at 37° C. and equilibrated forapproximately 5 min before addition of various agents. [Ca²⁺ i wascalculated using the following formula: ##EQU1##

All fluorescence values were measured relative to a EGTA-quenched signaldetermined as follows: F was the relative fluorescence measurement ofthe sample. F_(max) was determined by lysing the cells with digitonin(100ug/ml) in DMSO. After F_(max) was determined the pH was adjusted to8, with NaOH and Ca²⁺ chelated with 3mM EGTA to totally quench thefura-2 signal and obtain F_(min).

When quin-2- was used, cells were incubated with 10 uM quin-2- at 37° C.for 1 hour, washed and then used.

Mouse Ear Anti-Inflammatory Assay

Test compound and phorbol myristate acetate (PMA) are topically appliedsimultaneously to the pinnae of the left ears of mice. PMA alone isapplied to the right ear. Three hours and 20 minutes after application,the mice are sacrificed, left and right ears removed, and standard sizedbores taken. Edema (inflammation) is measured as the difference inweight between left and right ears [Van Arman, C.G., Clin Pharmacol Ther(1974) 16:900-904].

Inhibition of Phospholipase A₂

The effect of compounds made from the intermediate compounds of thisinvention on bee venom phospholipase A₂ is determined by the followingprocedure:

a. Bee venom phospholipase A₂ in 10 uM HEPES (pH 7.4) with 1 mM CaCl₂ isincubated with vehicle or test agent for 1.0 hour at 41°.

b. 1.36 mM phosphotidylcholine, 2.76 mM Triton X-100 are dispersed inbuffer by sonication and then mixed with L-3 phosphotidylcholine,1-palmitoyl-2-(1-¹⁴ C) palmitoyl for 10 min.

c. Start the reaction by the addition of enzyme (0.495 units/ml).

d. Incubation for 15 sec. at 41°.

e. Reaction is terminated by addition of 2.5 ml of isopropanol:n-heptane: 0.5 M H₂ SO₄ (40:10:1; v:v:v:).

f. 2.0 ml n-heptane and 1.0 ml H₂ O added; mixture centrifuged.

g. 2.0 ml n-heptane removed and treated with 200-300 mg of silica gelHR60.

h. Samples centrifuged; 1 ml of n-heptane SN removed and

added to 10 ml scintillation fluid.

i. Samples counted on a sointillation counter.

Inhibition of Phosphoinositide-specific Phospholipase C

The effect of compounds made from the intermediate compounds of thisinvention on phosphoinositide-specific phospholipase C may be determinedby procedures described by Bennett et al, Molecular Pharmacology32:587-593 (1987).

Specific Embodiments

Specific examples and procedures for preparing the compounds of theinvention, as well as specific examples and procedures for preparingfrom the compounds of the invention the biologically activeanti-inflammatory compounds, are provided below.

Generally speaking, and by way of general example and not limitation,the intermediate compounds embraced by Formula 1 which have one or moreOH, NH₂ or SH groups are subjected to one or more steps of alkylation,acylation, sulphonylation or phosphorylation or like reaction. Compoundsembraced by Formula 1 which have a functional group subject to aGrignard - lithium halide or like reaction (such as an aldehyde or estergroup) or subject to a Wittig (or like reaction), are reacted with asuitable reagent, followed, if desired, by acylation, sulphonylation andthe like of alcohol (OH) or amino (NH₂) functions in the side chain. Theresulting 2-trialkylsilyfuran intermediates, (which have in the 4position of the furan nucleus the side chain which is desired forbiological activity) are subjected to oxidation by singlet oxygen toprovide the biologically active 4-substituted5-hydroxy-2-(5H)-furanones. The conditions of the reactions with singletoxygen are described in detail in connection with several specificexamples. In general terms, these oxidation reactions are preferablyconducted in a mixture of water and acetone or in a mixture of water andtetrahydrofuran, and in some instances in substantially neattetrahydrofuran, in the presence of a catalyst, preferably Rose Bengaldye (preferably polymer bounded), which is added to the reactionmixture. The reaction mixture and vessel is flushed with oxygen and thereaction is conducted at low temperature, at approximately -78° C., orfor the herein described reactions preferably at approximately 0° C.,under a constant positive pressure of oxygen for a number of hours,typically 1 to 7 hours. The mixture is typically irradiated with a 150Watt flood lamp. Work-up of the reaction mixture after irradiationusually includes concentration by evaporation of the solvent, followedby chromatography on silica gel, in columns or on preparative silicaplates. ##STR7##

By way of further general examples, 2-triethylsilyl-4-hydroxymethylfuran(Compound 1; in Formula 1 R₁ ═R₂ ═R₃ ═CH₃ CH₂ --, X═OH and R₄ ═H) or thecorresponding trimethylsilyl compound, are utilized to make compounds ofFormula 5, where Y₁ is alkyl having at least 6 carbon atoms, arylalkyl,aryl, substituted aryl, substituted arylalkyl, alkenyl containing one ormore olephinic bonds and at least 6 carbon atoms, CO--R₃, CO--OR₃,CONHR₃, SO₂ R₃, SO₂ NHR₃ where R₃ is aryl, (such as phenyl or naphthyl)substituted aryl, (such as halogen or alkyl substituted phenyl ornaphthyl) substituted arylalkyl, (such as phenyl or naphthyl (C₁ -C₆alkyl)) alkyl of 1 to 20 carbons, alkenyl containing one or moreolephinic bonds; further Y is (CH₂)_(n) --O--R₄, or (CH₂)_(n)--O--(CH₂)_(m) --O--R₄, where n, and m, are integers and areindependently 1 to 25 and R₄ is phenyl, substituted phenyl or alkyl ofone to 20 carbons; still further Y is PO(OH)₂, PO(OH)OR₅, PO(OH)R₅PO(OR₅)₂, where R₅ is independently phenyl, substituted phenyl, alkyl of1 to 20 carbons or R₅ is (CH₂)_(n) --N(R₅ ^(*))₃ where R₅ ^(*) is alkylof 1 to 20 carbons. ##STR8##

2-Triethylsilyl-4-aminomethylfuran (Compound 2, in Formula 1 R₁ ═R₂ ═R₃═CH₃ CH₂ --, X═NH₂ and R₄ ═H) or the corresponding trimethylsilylcompound are utilized to make compounds of Formula 6, where Y₂ isdefined the same as Y₁ in connection with Formula 5. ##STR9##

2-Triethylsilyl-4-(1-hydroxy-tridecyl)-furan (Compound 3; in Formula 1R₁ ═R₂ ═R₃ ═CH₃ CH₂ --, X═OH and R₄ ═CH₃ (CH₂)₁₁ --) or thecorresponding trimethylsilyl compound are utilized to make compounds ofFormula 7 where Y₃ is H, C₁ -C₂₀ alkanoyl, trihaloacetyl, cyclohexanoyl,benzoyl, phenyl(C₁₋₄ alkanoyl), phenyl(C₂ -C₁₄ alkenoyl), naphthoyl, orcarbamoyl optionally N-substituted by one or two C₁₋₄ alkyl groups or byone alpha(C₁ -C₄ alkyl)benzyl group. ##STR10##

2-Triethylsilyl-4-(1-amino-tridecyl)-furan (Compound 4: in Formula 1 R₁═R₂ ═R₃ ═CH₃ CH₂ --, X═NH₂ and R₄ ═CH₃ (CH₂) ₁₁ --) or the correspondingtrimethylsilyl compound are utilized to make compounds of Formula 8where Y₄ is H, COR₃, SO₂ R₈, PO(OR₇)R₈, PS(OR₇)R_(8;) R₃ is C₁ -C₄alkyl, C₁ -C₄ alkoxy, trifluoromethyl, R₆ -(C₁ -C₄ alkyl), NHR₈ or N--R₉R₁₀ ; R₆ is carboxy, C₁ -C₄ alkoxycarbonyl, halo or CONR₁₁ R₁₁ ; R₇ ishydrogen or C₁ -C₄ alkyl or phenyl; R₈ is C₁ -C₄ alkyl, alkoxy having1-4 carbons, hydroxy, hydrogen or C₁ -C₆ alkanoyl; R₉ is H or C₁ -C₄alkyl; R₁₀ is H, C₁ -C₄ alkyl or SO₂ NR₂ R₂ ; and R₁₁ is H or C₁ -C₄alkyl. ##STR11##

3-(2-Triethylsilyl-4-furyl)propan-1-al (Compound 5; in Formula 1 R₁ ═R₂═R₃ ═CH₃ CH₂ --, X═H and R₄ ═CH₂ CHO) or the correspondingtrimethylsilyl compound are utilized to make compounds of Formula 9,where Y₅ is C₇ -C₁₄ alkyl, C₇ -C₁₄ alkoxide, N(C₁ -C₁₄ alkyl)₃--(CH₂)₂₋₈ Z or CCM; Z is H or CO₂ H and M is C₇ -C₁₄ alkyl; phenyl(C₁-C₄ alkyl) optionally substituted on the phenyl ring by 1-3 halosubstituent; M is further pyridyl(C₁ -C₄ alkyl), or naphthyl(C₁ -C₆alkyl). ##STR12##

2-Triethylsilyl-4-(1,2-dihydroxy-ethyl)furan (Compound 6; in Formula 1R₁ ═R₂ ═R₃ ═CH₃ CH₂ --, X═OH and R₄ ═CH₂ OH) or the correspondingtrimethylsilyl compound are utilized to make compounds of Formula 10where Y6 is H, C₁ -C₁₄ ═alkanoyl, CONHR₃, or CO₂ R_(4;) R₃ is phenyl orC₁ -C₄ alkyl; R₄ is C₁ -C₆ alkyl; and Y₇ is C₇ -C₁₄ alkanoyl, N-(C₆ -C₁₄alkyl) carbamoyl, naphthyl-(C₁ -C₆ alkyl), pyridyl-(C₁ -C₆ alkyl) andmethoxyethoxymethoxymethyl. ##STR13##

2-Triethylsilyl-4-(1-hydroxy-2-amino-ethyl)furan (Compound 7; in Formula1 R₁ ═R₂ ═R₃ ═CH₃ CH₂ --, X═OH and R₄ ═CH₂ NH₂) or the correspondingtrimethylsilyl compound are utilized to make compounds of Formula R₁₁where Y₈ is H, R₃, CO--R₃, CO--O--R₃, CO--NH--R₃, CO--N--(R₃)₂, PO(OR₃)₂or PO(OR₃)R₃, and R₃ independently is H, phenyl, substituted phenyl,alkyl of 1 to 20 carbons or is alkyl of 1 to 20 carbons substituted witha hydroxyl, alkoxy, substituted amino, thioalkoxy or with a COR₃ ^(*)group where R₃ ^(*) is H, lower alkyl, OH, OR₃ ^(**), NH₂, NHR₃ ^(**) orN(R₃ ^(**))₂ group where R₃ ^(*) independently is H or lower alkyl, withthe proviso that when Y₈ is CO--O--R₃ or is CO--NH--R₃ then R₃ is nothydrogen; Y₉ is H, R₄, CO--R₄, CO--O--R₄, CO--N-piperazinyl,CO--N--substituted N--piperazinyl, CO--N-morpholinyl, CO--N--substitutedN-morpholinyl, CO--NH--R₄, or CO--N(R₄)₂, PO(OR₄)₂, PO(OR₄)R₄, SO₂ OR₄,or SO₂ R₄, where R₄ independently is H, phenyl or substituted phenyl, oralkyl of 1 to 20 carbons, or is alkyl of 1 to 20 carbons substitutedwith a hydroxyl, alkoxy, substituted amino, thioalkoxy or with a COR₄^(*) group where R₄ ^(*) is H, lower alkyl, OH, OR₄ ^(**), NH₂, NHR₄^(**) or N(R₄ ^(**))₂ group where R₄ ^(**) is lower alkyl with theproviso that when Y₉ is CO--O--R₄ then R₄ is not hydrogen, and Y₁₀ is Hor alkyl of 1 to 20 carbons. ##STR14##

2-Triethylsilyl-4-(1,2-diamino-ethyl)furan (Compound 8; in Formula 1 R₁═R₂ ═R₃ ═CH₃ CH₂ --, X═NH₂ and R₄ ═CH₂ NH₂) or the correspondingtrimethylsilyl compound are utilized to make compounds of Formula 12where Y₁₁ and Y₁₂ are both independently defined as COR, CONHR, CO₂ R orSO₂ R and R is C₁ -C₂₀ -alkyl, aryl, aryl-(C₁ -C₂ -alkyl)-. ##STR15##

2-Triethylsilyl-4-iodomethylfuran (Compound 9; in Formula 1 R₁ ═R₂ ═R₃═CH₃ CH₂ --, X═I and R₄ ═H) or the corresponding trimethylsilyl compoundare utilized to make compounds of Formula 13 where p is an integerbetween zero and 2, and Y₁₃ is alkyl having 6 to 25 carbon atoms,arylalkyl, aryl, (such as phenyl) substituted aryl, (such as halogen oralkyl substituted phenyl) arylalkyl (such as phenyl (C₁ -C₆ alkyl),substituted arylalkyl, alkenyl containing one or more olephinic bondsand at least 6 carbon atoms, CO--R₃, CO--OR₃, CONHR₃, where R₃ is aryl,(such a phenyl or naphthyl) substituted aryl (such as halogen or alkylsubstituted phenyl or naphthyl), aralkyl (such as phenyl or (naphthyl C₁-C₆ alkyl))substituted arylalkyl, alkyl, alkenyl containing one or moreolephinic bonds, further Y₁₃ is (CH₂)_(n) --O--R₄, or (CH₂)_(n)--O--(CH₂)_(m) --O--R₄, where n, and m, are integers and areindependently 1 to 25 and R₄ is phenyl, substituted phenyl or alkyl ofone to 20 carbons, still further Y₁₃ is PO(OH)₂, PO(OH)OR₅, PO(OH)R₅,PO(OR₅)₂, where R₅ is independently phenyl, substituted phenyl, alkyl of1 to 20 carbons or R₅ is (CH₂)_(n) --N(R₅ ^(*))₃ where R₅ ^(*) is alkylof 1 to 20 carbons, or Y₁₃ is NH--R₆ where R₆ is phenyl, substitutedphenyl or alkyl of at least 6 carbon atoms with the provisos that when pis zero, then Y₁₃ is not NH--R₆, and when p is 1 or 2 then Y₁₃ is notPO(OH)₂, PO(OH)OR₅, PO(OH)R₅ or PO(OR₅)₂. ##STR16##

Still speaking generally and by way of general example, the intermediatecompounds embraced by Formula 2 can be subjected to hydrogenation,trans-esterification and other reactions involving the ethylenic doublebond or ester functionality (which reactions are otherwise known in theart), and can be subjected to oxydation by singlet oxygen to provide,for example, compounds of Formula 14 and of Formula 15. The conditionsfor oxydation with singlet oxygen are similar or identical to thosedescribed in connection with "singlet oxygen oxydation" of the compoundsof Formula 1. In Formula 14 and in Formula 15 the symbol R₅ is definedas alkyl of 1 to 20 carbons. The compounds of Formula 2 (such asCompound 10) are also used to make Compound 5, which is a startingmaterial for the preparation of compounds of Formula 9. ##STR17##

Still further, by way of general example, the intermediate compoundsembraced by Formula 3A include an aldehyde function in the 4-position ofthe furan nucleus. The aldehyde function can be subjected to a Grignard(or like) reaction with a Grignard reagent derived for example from along chain alkyl halide, and the resulting secondary alcohol (in theside chain of the 4-position of the furan nucleus) may be alkylated,acylated, phosphorylated, reacted with an alkyl, aralkyl or arylsulfonyl halide, or with an isocyanate to yield a carbamoyloxy group.Similarly, the intermediate compounds of Formula 3B can be alkylated,acylated, phosphorylated, reacted with an alkyl, aralkyl or arylsulfonylhalide, or with an isocganate. Oxidation by singlet oxygen ofthese derivatives, derived from the compounds of Formula 3A and 3B isconducted under conditions identical or substantially similar to theconditions described before. The oxidation reaction with singlet oxygenthus provides the exemplary compounds of Formula 16 where R₆ is phenyl,alkyl of 1 to 6 carbons and n is 1 or 2, and where the R₆ group isattached either to the 3 or to the 5 position of the 2(5H)-furanone; orwhen n is 2 then R₆ is attached to both the 3 and 5 positions. Y₁₄ is Hor an alkyl group, (preferably long chain alkyl), aryl (such as phenylor naphthyl), substituted aryl (such as halogen or alkyl substitutedphenyl or naphthyl) arylalkyl (such as phenyl (C₁ -C₆ alkyl) ornaphthyl(C₁ -C₆ alkyl)). Y₁₅ is defined the same as Y₁ in connectionwith Formula 5.

The synthetic intermediate compounds embraced by Formula 4A are2-trialkylsilyl-3-furaldehydes. The intermediate compounds embraced byFormula 4B are 2-trialkylsilyl-3-furylmethanols. By way of generalexample and not by way of limitation, the aldehyde function of thecompounds of Formula 4A is reacted in accordance with the invention,with a Grignard (or like) reagent derived for example from a long chainalkyl halide, and the resulting secondary alcohol (in the side chain ofthe 3-position of the furan nucleus) may be alkylated, acylated,phosphorylated, reacted with an alkyl aralkyl or aryl sulfonyl halide,or with an isocyanate to yield a carbamoyloxy group. The alkylation,acylation, phosphorylation and the other reactions just noted can alsobe carried out on the primary hydroxyl group of the compounds of Formula4B. Oxidation by singlet oxygen of these derivatives, derived from thecompounds of Formula 4A and 4B is conducted under conditions identicalor substantially similar to the conditions described before, and yields3-substituted 5-hydroxy-2(5H)-furanone derivatives. The latter arereduced, for example with sodium borohydride to yield the 3-substituted2(5H)-furanone compounds of Formula 17. ##STR18## In Formula 17 Y₁₆ isH, an alkyl group, (preferably long chain alkyl), aryl (such as phenylor naphthyl), substituted aryl (such as halogen or alkyl substitutedphenyl or naphthyl) arylalkyl (such as phenyl (C₁ -C₆ alkyl) ornaphthyl(C₁ -C₆ alkyl)).

Y₁₇ is H, alkyl of 1 to 20 carbons, arylalkyl, (such as phenyl (C₁ -C₆alkyl) or naphthyl(C₁ -C₆ alkyl)) aryl, (such as phenyl or naphthyl),substituted aryl (such as halogen or alkyl substituted phenyl ornaphthyl), substituted arylalkyl, alkenyl containing one or moreolephinic bonds, PO(OH)₂, PO(OH)OR₂, PO(OH)R₂ PO(OR₂)₂, where R₂ isindependently alkyl of 1 to 20 carbons, phenyl, or substituted phenyl,further Y₁₇ is CO--R₃, CO--OR₃, CONHR₃, SO₂ R₃, SO₂ NHR₃, (CH₂)_(n)--O--R₃, or (CH₂)_(n) --O--(CH₂)_(m) --O--R₃, where n, and m, areintegers and are independently 1 to 20 and R₃ is H, alkyl, alkenylcontaining one or more olephinic bonds, aryl, substituted aryl,arylalkyl or substituted arylalkyl, with the proviso that when Y₁₇ isCO--R₃, CO--OR₃, and CONHR₃ then R₃ is not hydrogen.

Alternatively, the synthetic intermediate compounds embraced by Formula4A (2-trialkylsilyl-3-furaldehydes) can also be used for the preparationof compounds shown in Formula 18, which are the "amino" analogs of thecompounds of Formula 17. The compounds of Formula 18 can be preparedfrom the compounds of Formula 4A by replacing the secondary alcoholformed after a Grignard reaction of the compounds of Formula 4, with anamino group. This can be accomplished, for example, by reacting thesecondary alcohol (obtained from the Grignard or like reaction) withdiphenylphosphoryl azide in the presence of diethyl azidodicarboxylate(DEAD), followed by reduction of the azide function to amino function.The symbols Y₁₆ and Y₁₇ in Formula 18 signify the same groups as inFormula 17. Generally speaking, the anti-inflammatory compounds madefrom the synthetic intermediates of Formula 4A are selective inhibitorsof calcium²⁺ channel mobilization.

Additional preferred compounds of the invention are2-methyl-4-phenyl-3-furaldehyde (Compound 16) the corresponding alcohol,2-methyl-4-phenyl-3-furylmethanol (Compound 17) 3-phenyl-4-furaldehyde(Compound 18) and 3-phenyl-4-furylmethanol (Compound 19). The specificexamples described below show how compounds 16 through 19 are used asintermediates for the synthesis of furanone compounds havinganti-inflammatory utility.

The synthetic chemist will appreciate the compounds of the invention, aswell as the biologically active anti-inflammatory compounds which aremade from the compounds of the invention, can be made in accordance withthe general procedures outlined above, and that the specific conditionsdescribed below are illustrative of these procedures and can begeneralized to make any and all compounds of the invention, as well asthe biologically active compounds derived therefrom.

SPECIFIC EXAMPLES EXAMPLE 1 2-Trimethylsilyl-4-furaldehyde

D-Butyl lithium (a 2.5M solution in hexane; 28.8 ml, 72 mmol) was addedto a solution of morpholine (6.28 ml, 72 mmol) in tetrahydrofuran (700ml) at -78° under argon. After 20 minutes, 3-furaldehyde (7.0 g, 72mmol) was added. After another 20 minutes, sec-butyl lithium (a 1.3Msolution in cyclohexane; 55.4 ml, 72 mmol) was added dropwise andstirring continued at -78° for 7 hours before trimethylsilyl chloride(27 ml, 216 mmol) was added. Stirring was continued overnight (14 hours)while the cooling bath was allowed to attain room temperature. Thesolution was poured into ice cold 10% (v/v) hydrochloric acid (200 ml)and after stirring at 0° for 10 minutes, the layers were separated. Theaqueous phase was extracted with diethyl ether. All the organic phaseswere combined, dried (magnesium sulfate) and evaporated to dryness togive a light brown oil, which was purified by flash chromatography onsilica using 2% ethyl ether/hexane. Fractions with R_(f) of about 0.30(silica, 10% ethyl ether/hexane) on evaporation gave the title aldehydeas a light yellow oil, b.p. 48°-50 °/0.25 torr.

¹ H NMR (CDCl₃) 0.29 (s, 9H), 6.98 (s, 1H), 8.25 (s, 1H) and 9.95 (s,1H).

¹³ C NMR (CDCl₃) -2.0, 116.2, 128.9, 155.3, 164.1 and 184.5.

HRMS exact mass calculated for C₈ H₁₂ O₂ Si(M⁺) 168.0607, found168.0588. See also U.S. Pat. No. 4,935,530, the specification of whichis incorporated herein by reference.

4-Hydroxymethyl-2-trimethylsilylfuran

2-Trimethylsilyl-4-furaldehyde (1.57 g, 9.35 mmol) was added to asuspension of sodium borohydride (424 mg, 11.2 mmol) in methanol (10 ml)at 0° C. After 45 minutes, most of the methanol was evaporated and theresidue taken up in ethyl ether. The ethyl ether extracts were combined,washed (water), dried (magnesium sulfate) and evaporated to dryness togive an oil, which was purified by flash chromotography on silica using30% ethyl ether/hexane to give the title alcohol as a pale yellow oil.

¹ H NMR (CDCl₃): 7.57 (s, 1H); 6.64 (s, 1H); 4.50 (s, 2H); 2.75 (broads, 1H); 0.25 (s, 9H).

¹³ C NMR (CDCl₃); 161.5, 144.0, 125.0, 119.7, 56.2, -1.8.

HRMS exact mass calculated for C₈ H₁₄ O₂ Si; 170.0763, obtained (EI⁺):170.0766.

2-Triethylsilyl-4-furaldehyde

n-Butyl lithium (a 2.5M solution in hexane; 30.6 ml, 76.5 mmol) wasadded to a solution of morpholine (6.66 ml, 76.5 mmol) intetrahydrofuran (500 ml) at -78° under argon. After 15 minutes,3-furaldehyde (6.3 ml, 72.8 mmol) was added. After another 20 minutes,sec-butyl lithium (a 1.3M solution in cyclohexane; 59.0 ml, 76.5 mmol)was added dropwise and stirring continued at -78° for about 2 hoursbefore triethylsilylchloride (13.4 ml, 80.1 mmol) was added. Stirringwas continued overnight (14 hours) while the cooling bath was allowed toattain room temperature. The solution was poured into ice cold 10% (v/v)hydrochloric acid (100 ml) and after stirring at 0° for 10 minutes, thelayers were separated. The aqueous phase was extracted with diethylether. All the organic phases were combined, dried (magnesium sulfate)and evaporated down to give an oil, which was distilled under highvacuum to give the 5-triethylsilyl-3-furaldehyde as a pale yellow oil,boiling point 85°-90°/0.4 torr.

IR (neat) 1680cm⁻¹

¹ H NMR (CDCl₃) 0.79 (q, 6H, J=7.3 Hz), 0.90 (t, 9H, J=7.3 Hz), 7.0 (s,1H), 8.26 (s, 1H) and 9.95 (s, 1H).

¹³ C NMR (CDCL₃) 2.9, 7.1, 117.2, 128.8, 155.6, 162.3 and 184.6.

HRMS m/e exact mass calculated for C₁₁ H₁₈ O₂ Si(M⁺) 210.1076, found210.1071 See also U.S. Pat. No. 4,935,530, the specification of which isincorporated herein by reference.

4-Hydroxymethyl-2-triethylsilylfuran (Compound 1)

Sodium borohydride (353 mg, 0.93 mmol) was added portionwise to asolution of 2-triethylsilyl-4-furaldehyde (1.64 g, 7.79 mmol) inmethanol (10 ml) at 0°. After 1 hour, most of the methanol wasevaporated and the residue dissolved in a minimum amount of dilutehydrochloric acid. Extraction (ethyl acetate), drying (magnesiumsulfate) and evaporation gave an oil, which was purified by flashchromatography on silica using 20% ethyl ether/hexane. Fractions withR_(f) of about 0.07 (10% ethyl ether/hexane) gave after evaporation thetitle alcohol as a colorless oil.

¹ HNMR (CDCl₃) 0.76 (q, 6H, J=7.4 Hz), 0.97 (t, 9H, J=7.5 Hz), 1.45 (t,1H, J=5.3 Hz), 4.56 (d, 2H, J=5.3 Hz), 6.67 (s, 1H) and 7.62 (s, 1H).

HRMS exact mass calculated for C₁₁ H₂₀ SiO₂ (M⁺) 212.1233 found212.1231.

2-(tert-Butyldimethylsilyl)-4-furaldehyde

n-Butyl lithium (a 2.5 M solution) in hexane; 8.3 ml, 20.8 mmol) wasadded to a solution of morpholine (1.81 ml, 20 mmol) in tetrahydrofuran(100 ml) at -78° C. under argon. After 20 minutes 3-furaldehyde (1.8 ml,20.8 mmol) was added. After another 15 minutes, sec-butyl lithium (a1.3M solution in cyclohexane; 16.8 ml, 21.9 mmol) was added dropwise andstirring continued at -78° C. for 1 hour before a solution oft-butyldimethylsilyl chloride (9.4 g, 62.4 mmol) in tetrahydrofuran (10ml) was added. Stirring was continued overnight (16 hours) while thecooling bath was allowed to attain room temperature. The solution waspoured into ice cold 10% (v/v) hydrochloric acid (40 ml) and afterstirring at 0° for 10 minutes, the layers were separated. The aqueousphase was extracted with diethyl ether. All the organic phases werecombined, dried (magnesium sulfate) and evaporated to dryness to give abrown oil, which was distilled under high vacuum to give the titlealdehyde, boiling point 80°-5°/0.5 torr., m.p. 37-8.

¹ H NMR (CDCl₃) 0.23 (s, 6H), 0.90 (s, 9H), 6.99 (s, 1H), 8.25 (s, 1H)and 9.94 (s, 1H).

¹³ C NMR (CDCl₃) 16.6, 26.1, 117.3, 128.8, 155.5, 162.7 and 184.5.

HRMS exact mass calculated for C₁₁ H₁₈ O₂ Si (M⁺) 210.1076, found210.1075.

4-(Methoxyethoxymethoxymethyl)-2-trimethylsilylfuran

2-Methoxyethoxymethyl chloride (0.11 ml, 0.96 mmol) was added to asolution of 4-hydroxymethyl-2-trimethylsilylfuran, also known as(2-tirmethylsilyl-4-furyl)methanol, (162.8 mg, 0.96 mmol) anddimethylaniline (0.13 ml, 0.1 mmol) in dichloromethane (5 ml) at 0°.After stirring at room temperature overnight (ca. 16 hours), thereaction mixture was washed successively with water, dilute hydrochloricacid and water. Evaporation of the dried (magnesium sulfate)dichloromethane layer gave an oil, which was purified by preparativesilica TLC (developed with 30% ethyl ether/hexane) to give the titleether as a colorless oil.

¹ H NMR (CDCl₃) 0.27 (s, 9H), 3.44 (s, 3H), 3.62 (m, 2H), 3.76 (m, 2H),4.51 (s, 2H), 4.79 (s, 2H), 6.67 (s, 1H), and 7.65 (s, 1H). MS m/e (%abundance 258(M⁺, 23), 182(19), 169(57), 154(72), 153(80), 89(50),73(100) and 59(33).

4-Methoxyethoxymethoxymethyl)-5-hydroxy-2(5H)-furanone (Compound 20)

A mixture of 4-(methoxyethoxymethoxymethyl)-2-trimethylsilylfuran (106mg, 0.41 mmol) and Rose Bengal (co. 3.0 mg) in tetrahydrofuran (7 ml)was exposed to singlet oxygen at -78° for 2 hours. The residue, aftersolvent removal, was purified by chromatography on preparative silicathin layer plates (developed with 40% ethyl acetate/hexane) to give thetitle furanone as a colorless oil.

¹ HNMR (CDCl₃) 3.43 (s, 3H), 3.61, 3.75 (2 br s, 4H), 4.51 (s, 2H), 4.84(s, 2H) and 5.30 (br, 1H), 6.11 (s, 1H) and 6.14 (s, 1H).

¹³ C NMR (CDCl₃) 58.9, 62.7, 67.1, 71.6, 95.9, 97.8, 118.7, 165.3 and170.6.

4-(dodecylphosphonyloxymethyl)-2-triethylsilylfuran

Dodecylphosphinic dichloride (944 mg, 3.29 mmol) was added to a solutionof 4-hydroxymethyl-2-triethylsilylfuran (Compound 1, also known as(2-triethylsilyl-4-furyl)methanol 696.8 mg, 3.29 mmol) and4-dimethylaminopyridine (403 mg, 3.29 mmol) in tetrahydrofuran (5 ml) at0°. After stirring at room temperature overnight (15 hours), a solutionof potassium hydroxide (235 mg, 3.62 mmol) in water (ca. 3 ml) wasadded. After 30 minutes, the solution was diluted with water andextracted thoroughly with ethyl acetate. Evaporation of the dried(magnesium sulfate) extracts gave an oil, which was purified by flashchromatography on silica using 40% ethyl ether/hexane to give the titleester as a pale yellow oil.

¹ HNMR (CDCl₃) 0.75 (q, 6H, J=8.1 Hz), 0.90 (t, 3H, J=6.9 Hz), 0.99 (t,9H, J=7.8 Hz), 1.27 (br s, 18H), 1.55 (m, 2H), 1.90 (m, 2H), 4.90 (m,2H), 6.70 (s, 1H) and 7.68 (s, 1H).

MS m/e (% abundance) 444(M⁺, 12), 388(100), 335(22), 195(21) and115(21).

4-(Dodecylphosphonyloxymethyl)-5-hydroxy-2(5H)-furanone (Compound 21)

A mixture of 3-(dodecylphosphonyloxymethyl)-5-triethylsilylfuran (325mg, 0.73 mmol), Rose Bengal (ca. 5 mg) and water (ca. 0.05 ml) intetrahydrofuran (10 ml) was exposed to singlet oxygen at 0° C. for 1.5hours. The residue, after solvent removal, was purified bychromatography on preparative silica thin layer plates (developed with5% methanol/dichloromethane) to give the title furanone.

¹ HNMR (CDCl₃) 0.91 (t, 3H, J=6.2 Hz), 1.29 (br s, 16H), 1.40 (m, 2H),1.65 (br m, 1H), 1.95 (m, 1H), 4.95 (br, 2H), 6.15 (br s, 1H), 6.18 (brs, 1H) and 7.0 (br, 1H).

¹³ CNMR (CDCl₃) 13.9, 21.9, 22.5, 23.9, 25.7, 28.7, 28.9, 29.2, 29.3,29.5, 30.2, 30.5, 31.7, 60.8, 97.5, 118.6, 163.3, 163.4 and 170.4.

FABMS (negative ion) 361[(M-H)⁺, 9] and 249(72).

4-(N-Dodecylcarbamoyloxymethyl)-2-triethylsilylfuran

Potassium bis(trimethylsilyl)amide (a 0.5M solution in toluene; 0.7 ml,0.36 mmol) was added to a solution of4-hydroxymethyl-2-triethylsilylfuran (Compound 1, 76.1 mg, 0.36 mmol) intetrahydrofuran (2ml) at 0° under argon. After 30 minutes, a solution ofdodecylisocynate (151 mg, 0.72 mmol) in tetrahydrofuran (0.5 ml) wasadded. Stirring was continued overnight (14 hours) while the coolingbath attained room temperature. The reaction mixture was quenched withwater and extracted thoroughly with ether. Evaporation of the dried(magnesium sulfate) extracts gave an oil, which was purified bypreparative silica TLC (developed with 10% ethyl ether/hexane) to givethe title carbonate as a pale yellow oil.

¹ HNMR (CDCl₃) 0.77 (q, 6H, J=8.0 Hz), 0.91 (t, 3H, J=6.9 Hz), 1.00 (t,9H, J=7.3 Hz), 1.29 (br s, 18H), 1.50 (m, 2H), 3.20 (m, 2H), 4.72 (br,1H), 5.00 (br s, 2H), 6.69 (s, 1H) and 7.69 (s, 1H).

HRMS exact mass calculated for C₂₄ H₄₅ SiNO₃ (M⁺) 423.3168, found423.3164.

4-(N-Dodecylcarbamoyloxymethyl)-5-hydroxy-2(5H)-furanone (Compound 22)

A mixture of 3-(N-dodecylcarbamoyloxymethyl)-5-triethylsilylfuran (80mg, 0.19 mmol), water (ca, 0.1 ml) and Rose Bengal (ca. 3 mg) intetrahydrofuran (5 ml) was exposed to singlet oxygen at 0° for 1.5hours. The residue, after solvent removal, was purified bychromatography on preparative silica thin layer plates (developed withethyl acetate) to give the title furanone as a colorless oil.

¹ HNMR (CDCl₃) 0.92 (t, 3H, J=6.8 Hz), 1.29 (br s, 20H), 1.55 (br m,2H), 3.20 (dd, 2H, J=6.3 Hz), 4.95 (br, 1H), 5.20 (br, 1H), 6.07 (br s,1H) and 6.16 (br s, 1H).

¹³ CNMR (CDCl₃) 13.8, 22.5, 26.5, 26.8, 29.6, 28.6, 28.7, 28 8, 29.0,29.1, 29.4, 29.6, 30.0, 31.7, 41.2, 59.4, 97.9, 118.6, 115.9, 164.4 and170.7.

4-Dodecanoxy-2-triethylsilylfuran

A solution of 4-hydroxymethyl-2-triethylsilylfuran (Compound 1, 160 mg,0.75 mmol) in tetrahydrofuran (0.5 ml) was added to a suspension ofpotassium hydride (33 mg, 0.83 mmol) in tetrahydrofuran (1 ml) at roomtemperature. When all the potassium hydride disappeared, 1-iodododecane(0.37 ml, 1.5 mmol) was added. Stirring was continued for 4 days at roomtemperature. The reaction mixture was quenched with water. Extraction(ethyl ether) and evaporation of the dried (magnesium sulfate) extractsgave an oil, which was purified by flash chromatography on silica using5% ethyl ether/hexane. Fractions with R_(f) of about 0.65 on evaporationgave the titled ether as a pale yellow oil.

¹ HNMR (CDCl₃) 0.76 (q, 6H, J=7.6 Hz), 0.91 (t, 3H, J=6.9 Hz), 1.00 (t,9H, J=7.3 Hz) 1.29 (br s, 18H), 1.65 (m, H), 3.47 (t, 2H, J=6.7 Hz),4.39 (s, 2H), 6.68 (s, 2H) and 7.63 (s, 1H).

HRMS exact mass calculated for C₂₃ H₄₄ O₂ Si(M⁺) 380.3111, found380.3100.

4-(Dodecanoxy)-5-hydroxy-2(5H)-furanone (Compound 23)

A mixture of 4-dodecanoxy-2-triethylsilylfuran (85 mg, 0.22 mmol), water(0.05 ml) and Rose Bengal (ca. 3 mg) in tetrahydrofuran (6 ml) wasexposed to singlet oxygen at 0° for 1.5 hours. The residue, aftersolvent removal, was purified by chromatography on preparative silicaplates (20×20cm, 1000u, developed with 50% ethyl ether/hexane) to givethe title furanone as a colorless solid.

¹ HNMR (CDCl₃) 0.92 (t, 3H, J=6.9 Hz), 1.30 (br s, 18H), 1.64 (m, 2H),3.57 (t, 2H, J=6.6 Hz), 4.37 (br s, 2H), 5.75 (br, 1H), 6.10 (s, 1H) and6.16 (s, 1H).

¹³ C NMR (CDCl₃) 14.1, 22.6, 25.9, 29.3, 29.4, 29.5, 29.6, 31.9, 65.7,71.9, 97.9, 117.9, 166.5 and 171.5.

HRMS exact mass calculated for C₁₇ H₃₁ O₄ (M+H)⁺ 299.2222, found299.2204.

Diethyl (2-triethylsilyl-4-furyl)methyl phosphate

A mixture of (2-triethylsilyl-4-furyl)methanol (Compound 1, 2.86 g, I3.5mmol), triethylamine (3.76 ml, 27.0 mmol) and diethyl chlorophosphate(4.28 ml, 29.0 mmol) in tetrahydrofuran (10 ml) was stirred at roomtemperature for 14 hours. The mixture was filtered and the filtrate wasevaporated to dryness to give a residue, which was redissolved in ethylether and washed with 10% hydrochloric acid, water and 5% sodiumbicarbonate. Evaporation of the dried (magnesium sulfate) organic phasegave an oil, which was purified by chromatography on a silica columnwith 30% ethyl acetate/hexane to give the title ester.

IR(CDCl₃): 1260 and 1220.

¹ HNMR (CDCl₃): 0.70 (q, 6H, J=7.8 Hz), 0.92 (t, 9H, J=7.8 Hz), 1.24 (t,6H, J=7.1 Hz), 4.01 (q, 2H, J=6.8 Hz), 4.03 (q, 2H, J-6.8 Hz), 4.90 (s,1H), 4.93 (s, 1H), 6.66 (s, 1H) and 7.64 (s, 1H).

¹³ CNMR (CDCl₃): 3.0 , 7.1, 15.8, 15.9, 60.6, 60.7, 63.5, 63.6, 120.5,120.6, 121.0, 145.5 AND 159.7

4-1-(Diethylphosphoryloxy)methyl-5-hydroxy-2(5H)-furanone (Compound 24)

A mixture of diethyl (2-triethylsilyl-4-furyl)methyl phosphate (803 mg,2.31 mmol), water (2 drops) and Rose Bengal (5 mg) in acetone (50 ml)was exposed to singlet oxygen at 0° for 7 hours. The residue, aftersolvent removal, was purified by chromatography on a silica column usingethyl acetate to give the title furanone.

IR (CHCl₃) 3250, 1770, 1250, 1150, 1050 and 960.

¹ HNMR (CDCl₃): 1.37 (t, 6H, J=6.0 Hz), 4.16 (2q, 4H, J =6.0 Hz), 4.85(ddd, 1H, J=15.0 Hz, 9.0 Hz, 1.2 Hz); 4.96 (ddd, 1H, J=15.0 Hz, 7.2 Hz;0.6 Hz), 6.12 (s, 1H) and 6.15 (s, 1H).

¹³ CNMR (CDCl₃): 62.1, 64.7, 97.4, 118.8, 163 3, 163.4 and 170.4.

4-Dodecoyloxymethyl-2-trimethylsilylfuran

To a stirred solution of 4-hydroxymethyl-2-trimethylsilylfuran (0.288g., 1.70 mmol) and pyridine (0.214 g., 2.55 mmol) in 30 ml drytetrahydrofuran at 0 degrees was added lauroyl chloride (0.408 g., 1.86mmol). This solution was allowed to warm to room temperature, stirred 30minutes, and partitioned between ethyl ether and 5% sodium bicarbonatesolution. The organic portion was washed with aqueous cupric sulfatesolution, water, saturated sodium chloride solution, dried overmagnesium sulfate, filtered and concentrated to a colorless oil. Thismaterial was purified by flash chromatography (silica, 5% ethylether/petroleum ether) to give the desired ester.

¹ H NMR (CDCl₃): 7.64 (s, 1H); 6.63 (s, 1H); 4.97 (s, 2H); 2.31 (t,J=7.3 Hz, 2H); 1.55 to 1.7 (m, 2H); 1.2 to 1.4 (m, 16H); 0.89 (t, J=6.3Hz, 3H); 0.25 (s, 9H).

¹³ C NMR (CDCl₃) 173.5, 161.4, 145.6, 120.3, 57.4, 34.2, 31 8, 29.5,29.4, 29.3, 29.2, 29.0, 24.9, 22.6, 14.0, -1.8.

m/z Calculated for C₂₀ H₃₆ O₃ Si: 352.2434, obtained (CI⁺): 352.2448.

4-Dodecoyloxymethyl-5-hydroxy-2(5H)-furanone

A stirred solution of 4-dodecoyloxymethyl-2-trimethylsilylfuran (0.375g., 1.07 mmol) and Rose Bengal (trace) in 275 ml of acetone was flushedwith oxygen and cooled to -78° degrees. The solution was subsequentlyirradiated with a 300 Watt flood lamp while under constant positivepressure of oxygen until starting material was no longer visible by TLC.The solution was warmed to room temperature and concentrated to a pale,orange solid residue. This material was purified by passing through asmall plug of silica (ethyl ether as eluent) to give the desiredhydroxybutenolide.

¹ H NMR (CDCl₃) 6.16 (broad s, 1H); 6.05 (broad s, 1H); 5.55 (broad s,1H); 4.97 (m, 2H); 2.41 (m, 2H); 1.6 to 1.75 (m, 2H); 1.2 to 1.4 (m,16H); 0.88 (m, 3H).

¹³ C NMR (CDCl₃): 173.4, 170.4, 163.2, 118.7, 97.6, 58.8, 33.9, 31.929.5, 29.4, 29.3, 29.2, 29.1, 24.8, 22.6, 14.1.

m/z Calculated for C₁₇ H₃₂ NO₅ (M+NH₄)⁺ : 330.2280, obtained (CI⁺):330.2282.

EXAMPLE 2 (E),(Z)-)-O-Methyl-2-triethylsilyl-4-furaldehyde oxime

A solution of sodium acetate (1 g, 12.3 mmol) and methoxylaminehydrochloride (1.05 g, 12.3 mmol) in water (5 ml) was added to asolution of 2-triethylsilyl-4-furaldehyde (860 mg, 4.1 mmol) in ethanol(6 ml) at room temperature. After stirring for 16 hours, most of theethanol was evaporated and the residue dissolved in water. Extraction(ethyl acetate) and evaporation of the dried (magnesium sulfate)extracts gave an oil, which was purified by flash chromatography onsilica using 5% ethyl ether/hexane to give the title oxime as acolorless oil.

¹ HNMR (CDCl₃) 0.79 (q, 6H, J=7.3 Hz), 0.99 (t, 9H, J=7.9 Hz), 3.95 (s,3H), 4.06 (s, 3H), 6.84 (s, 1H), 7.00 (s, 1H), 7.28 (s, 1H), 7.82 (s,1H), 8.05 (s, 1H) and 8.34 (s,

HRMS exact mass calculated for C₁₂ H₂₁ NO₂ Si(M⁺) 239.1341, found239.1332.

4-Aminomethyl-2-triethylsilylfuran (Compound 2)

Lithium aluminum hydride (a 1.0 M solution in tetrahydrofuran; 0.54 ml,0.54 mmol) was added dropwise to a solution of(E),(Z)-O-methyl-2-triethylsilyl-4-furaldehyde oxime (106.2 mg, 0.46mmol) in tetrahydrofuran (5 ml) at room temperature. After stirring atroom temperature overnight (ca. 14 hours), the reaction mixture wasquenched with water. Extraction (ethyl ether) and evaporation of thedried (magnesium sulfate) extracts gave an oil, which was purified byflash chromatography on silica using 10% methanol/dichloromethane/1%ammonia. Fractions with R_(f) of about 0.34 gave after evaporation thetitle amine as a pale yellow oil.

¹ H NMR (CDCl₃) 0.76 (q, 6H, J=7.9 Hz), 0.98 (t, 9H, J= 8.4 Hz), 1.87(br s, 2H), 3.76 (s, 2H), 6.63 (s, 1H) and 7.56 (s, 1H).

HRMS exact mass calculated for C₁₁ H₂₁ SiNO(M⁺) 211 1392, found211.1389.

4-(N-Dodecanoylaminomethyl-2-triethylsilylfuran

Dodecanoyl chloride (109 mg, 0.49 mmol) was added to a solution of4-aminomethyl-2-triethylsilylfuran (Compound 2, 70 mg, 0.33 mmol) andtriethylamine (69 microliter, 0.49 mmol) in tetrahydrofuran (3 ml) atroom temperature. After stirring at room temperature overnight (ca. 15hours), most of the solvent was evaporated and the residue was purifiedby chromatography on preparative silica thin layer plates (developedwith 50% ethyl ether/hexane) to give the title amide as a colorless oil.

¹ HNMR (CDCl₃) 0.75 (q, 6H, J=7.9 Hz), 0.87 (t, 3H, J=6.8 Hz), 0.97 (q,9H, J=7.9 Hz), 1.24 (br s, 16H), 1.60 (m, H), 2.17 (t, 2H, J=7.8 Hz),4.27 (d, 2H, J=5.3 Hz), 5.65 (br s, 1H), 6.57 (s, 1H) and 7.56 (s, 1H).

HRMS exact mass calculated for C₂₃ H₄₃ NO₂ Si(M⁺) 393.3063, found393.3048.

4-(N-Dodecanoylaminomethyl)-5-hydroxy-2(5H)-furanone (Compound 25)

A mixture of 4-(N-dodecanoylaminomethyl)-2-triethylsilylfuran (73.2 mg,0.18 mmol), water (0.05 ml) and Rose Bengal (ca. 3 mg) intetrahydrofuran (5 ml) was exposed to singlet oxygen at 0° for 1.5hours. The residue, after solvent removal, was purified bychromatography on preparative silica thin layer plates (developed withethyl acetate) to give the title furanone as an off-white solid.

1HNMR (CDCl₃) 0.93 (t, 3H, J=6.9 Hz), 1.30 (br s, 16H), 1.65 (br m, 2H),2.31 (t, 2H, J=7.8 Hz), 4.22 (d, 2H, J=5.0 Hz), 5.93 (s, 1H), 6.11 (s,1H) and 7.04 (t, 1H, J =5.0 Hz).

¹³ CNMR (CD₃ OD) 14.5, 23.7, 26.9, 30.3, 30.5, 30.6, 30.7, 33.0, 36.8,37.7, 100.0, 118.1, 168.7, 172.6 and 176.4.

HRMS exact mass calculated for C₁₇ H₃₀ NO₄ (M+H)⁺ 312.2174, found312.2182.

4-(N-Dodecylureido)methyl-2-triethylsilylfuran

Dodecylisocyanate (105 mg, 0.49 mmol) was added to a solution of4-aminomethyl-2-triethylsilylfuran (Compound 2, 70 mg, 0.33 mmol) andtriethylamine (69 microliter, 0.49 mmol) in tetrahydrofuran (3 ml) atroom temperature. After stirring at room temperature overnight (ca. 16hours), the reaction mixture was quenched with water. Extraction (ethylether) and evaporation of the dried (magnesium sulfate) extracts gave aresidue which was purified by flash chromatography on silica using 60%ethyl ether/hexane. Fractions of R_(f) of about 0.47 on evaporation gavethe title urea as an off-white solid.

¹ HNMR (CDCl₃) 0.74 (q, 6H, J=8.0 Hz), 0.87 (t, 3H, J=6.9 Hz), 0.96 (q,9H, J=7.7 Hz), 1.24 (br s, 18H), 1.40 (m, 2H), 3.15 (q, 2H, J=6.4 Hz),4.17 (d, 2H), J=5.4 Hz), 4.67 (br t, 1H), 4.85 (br t, 1H), 6.58 (s, 1H)and 7.53 (s, 1H).

HRMS exact mass calculated for C₂₄ H₄₆ N₂ O₂ Si(M⁺) 422.3329 found422.3315.

4-(N-Dodecylureido)methyl-5-hydroxy-2(5H)-furanone (Compound 26)

A mixture of 4-(N-dodecylureido)methyl-2-triethylsilylfuran (80 mg, 0.19mmol), water (0.01 ml) and Rose Bengal (ca. 3 mg) in tetrahydrofuran (6ml) was exposed to singlet oxygen at 0° for 1 hour. The residue, aftersolvent removal, was purified by chromatography on preparative silicathin layer plates (developed with ethyl acetate) to give the titlefuranone as a colorless solid.

¹ HNMR (CD₃ OD) 0.93 (t, 3H, J=7.2 Hz), 1.33 (br s, 18H), 1.50 (br t,2H), 3.16 (t, 2H, J=6.9 Hz), 4.12 (br s, 2H), 4.91 (s, 2H), 5.91 (br s,1H) and 6.09 (s, 1H).

¹³ CNMR (CD₃ OD) 14.5, 23.7, 27.9, 30.5, 30.8, 31.0, 31.3, 33.1, 38.6,41.1, 99.9, 117.6, 160.7, 170.7 and 172.8.

HRMS exact mass calculated for C₁₈ H₃₃ N₂ O₄ (M+H)⁺ 341.2440, found341.2434.

4-(N-Dodecylsulfonamido)methyl-2-triethylsilylfuran

Dodecanesulfonyl chloride (124 mg, 0.46 mmol) was added to a solution of4-aminomethyl-2-triethylsilylfuran (Compound 2, 81.3 mg, 0.39 mmol) andtriethylamine (64 microliter, 0.46 mmol) in tetrahydrofuran (2 ml) wasalso added. After stirring at room temperature overnight (ca. 18 hours),the reaction mixture was quenched with water. Extraction (ethyl ether)and evaporation of the dried (magnesium sulfate) extracts gave an oil,which was purified by chromatography on preparative silica thin layerplates (developed with 30% ethyl ether/hexane) to give the titlesulfonamide as a pale yellow oil.

¹ HNMR (CDCl₃) 0.74 (q, 6H, J=7.9 Hz), 0.88 (t, 3H, J=7.8 Hz), 0.95 (t,9H, J=7.4 Hz), 1.26 (br s, 18H), 1.75 (m, 2H), 2.94 (m, 2H), 4.17 (d,2H, J=5.9 Hz), 4.35 (t, 1H, J=5.9 Hz), 6.64 (s, 1H) and 7.63 (s, 1H).

4-(N-Dodecylsulfonamido)-methyl-5=hydroxy-2(5H)-furanone (Compound 27)

A mixture of 4-(N-dodecylsulfonamido)methyl-2-triethylsilylfuran (106mg, 0.24 mmol), water (0.01 ml) and Rose Bengal (ca 3 mg) intetrahydrofuran (6 ml) was exposed to singlet oxygen at 0° for 1.5hours. The residue, after solvent removal, was purified bychromatography on preparative silica thin layer plates (developed with50% ethyl acetate/hexane) to give the title furanone as a colorlesssolid.

¹ HNMR (CD₃ OD) 0.95 (t, 3H, J=6.8 Hz), 1.34 (br s, 16H), 1.50 (m, 2H),1.80 (m, 2H), 3.15 (m, 2H), 4.11 (br s, 2H), 4.92 (br s, 2H), 6.15 (s,1H) and 6.17 (s, 1H).

¹³ CNMR (CD₃ OD) 14.3, 23.6, 24.6, 29.2, 30.2, 30.4, 30.6, 30.7, 40.9,53.5, 100.2, 119.3, 168.9 and 172.9.

FABMS 362[(M+H)⁺, 18]

EXAMPLE 3 4-(1-Hydroxytridecyl)-2-trimethylsilylfuran

A mixture of 1-bromododecane (3.45 g, 14 mmol) and magnesium turnings(349 mg, 14.5 mmol) in tetrahydrofuran (10 ml) was refluxed under argonfor 1 hour. After cooling to 0 degrees, a solution of5-bromo-3-furaldehyde (2.42 g, 14 mmol) in tetrahydrofuran (3 ml) wasadded and conditions maintained or 20 minutes The mixture was furthercooled to -78 degrees and tert-butyl lithium (a 1.7 M solution inpentane; 9.77 ml, 1.67 mmol) was added dropwise, followed bychlorotrimethylsilane (5.27 ml, 41.5 mmol) after 20 minutes Stirring wascontinued overnight (12 hours) while the cooling bath attained roomtemperature. The mixture was quenched with saturated aqueous ammoniumchloride, diluted with water (15 ml) and extracted with ethyl ether.Evaporation of the dried (magnesium sulfate) extract gave a brown oil,which was flash chromatographed on silica using 15% ethylether/petroleum ether. Fractions with R_(f) of about 0.25 on evaporationafforded the title trimethylsilylfuran as a pale yellow oil.

¹ H NMR (CDCl₃): 0.26 (s, 9H), 0.91 (t, 3H, J=6.7 Hz), 1.29 (broad s,20H), 1.64 (br, 1H), 1.77 (m, 2H), 4.67 (t, 1H, J=6.8 Hz), 6.65 (s, 1H)and 7.59 (s, 1H).

MS m/e (% abundance) 339 (m⁺ +1, 9), 338 (31), 170 (35), 169 (100), 75(15) and 73 (50).

4-(1-Hydroxytridecyl)-5-hydroxy-2(5H)-furanone

A mixture of 4-(1-hydroxytridecyl)-2-trimethyl-silylfuran (271.2 mg, 0.8mmol) and Rose Bengal (5 mg) in tetrahydrofuran (10 ml) was exposed tosinglet oxygen for 2 hours at -78 degrees. The residue, after solventremoval, was flash chromatographed on silica using 70% ethylether/petroleum ether. Fractions with R_(f) of about 0.09 (60% ethylether/petroleum ether) on evaporation afforded the captioned furanone asa colorless oil.

¹ H NMR (CDCl₃): 0.91 (t, 3H, J=6.8 Hz), 1.29-1.34 (broad m, 20H), 1.75(m, 2H), 4.00 (br, 2H, exchanged with D20), 4.68 (m, 1H), 5.99 (s, 1H),6.10 (d, 1H, J=7.5 Hz, sharpened into a singlet on D₂ O exchange), 6.15(d, 1H, sharpened into a singlet on D₂ O exchange) and 6.28 (s, 1H).

¹³ C NMR (CDCl₃) 14.1, 22.7, 25.1 25.1, 25.7, 29.1, 29.3, 29.5, 29.6,29.6, 29.8, 31.9, 35.3, 35.6, 68.0, 68.2, 97.5, 97.6, 117.6, 118.1,168.9, 170.4, 170.6 and 170.9.

MS m/e exact mass calculated for C₁₇ H₃₁ O₄ (M+H)⁺ 299.2222, found299.2231.

4-(1-Acetoxytridecyl)-2-trimethylsilylfuran

A mixture of 4-(1-hydroxytridecyl)-2-trimethyl-silylfuran (1.32 g, 3.89mmol), acetic anhydride (4 ml) and pyridine (6 ml) was stirred underargon at ca. 20 degrees for 16 hours. After most of the solvent wasremoved under high vacuum (<40 degrees), the residue was dissolved inethyl ether (40 ml) and washed thoroughly with aqueous copper sulfateand water. Drying (magnesium sulfate) and evaporation gave a brown oil,which was flash chromatographed on silica using 5% ethyl ether/petroleumether. Fractions with R_(f) of about 0.55 (10% ethyl ether/petroleumether) on evaporation gave the desired trimethylsilylfuran as a paleyellow oil.

¹ H NMR (CDCl₃): 0.219 (s, 9H), 0.93 (t, 3H, J=6.8 Hz), 1.30 (broad s,20H), 1.90 (m, 2H), 2.09 (s, 3H), 5.81 (t, 1H, J=6.8 Hz), 6.63 (s, 1H)and 7.64 (s, 1H).

MS m/e (% abundance) 381 (M⁺ +1, 13), 380 (42), 346 (11), 339 (28), 338(100), 321 (29), 320 (17), 183 (23), 170 (36), 169 (29), 154 (26), 153(11), 117 (27), 75 (23) and 73 (90).

4-(1-Acetoxytridecyl)-5-hydroxy-2(5H)-furanone (Compound 28)

A mixture of 4-(1-acetoxytridecyl)-2-trimethylsilylfuran (314.2 mg, 0.83mmol) and Rose Bengal (5 mg) in tetrahydrofuran (7 ml) was exposed tosinglet oxygen for 2.5 hours at -78 degrees. The residue, after solventremoval, was flash chromatographed on silica using 45% ethylether/petroleum ether. Fractions with R_(f) of about 0.21 (60% ethylether/petroleum ether) on evaporation afforded the4-(1-acetoxytridecyl)-5-hydroxy-2(5H)-furanone as colorless prisms: mp67-8 degrees.

¹ H NMR (CDCl₃): 0.88 (t, 3H, J=7.5 Hz), 1.26 (broad s, 20H), 1.82 (m,2H), 2.11 (s, 3H), 2.14 (s, 3H), 4.06 (broad d, 1H, exchanged with D₂O), 4.86 (broad d, 1H, exchanged with D₂ O), 5.36 (t, 1H, J=5.6 Hz),5.50 (t, 1H, J=5.6 Hz), 5.95 (s, 1H), 5.99 (s, 1H), 6.00 (d, 1H, J=10Hz) and 6.19 (d, 1H, J=7.5 Hz).

¹³ C NMR (CDCl₃): 14.1, 20.8, 22.7, 25.0, 25.1, 29.2, 29.3, 29.3, 29.5,31.9, 33.0, 33.2, 69.2, 69.8, 98.0, 118.5, 119.2, 167.1, 169.8, 170.7and 171.2.

MS m/e: exact mass calculated for C₁₉ H₃₆ O₅ N (M+HN₄)⁺ 358.2593, found358.2597.

4-(1-Methoxytridecyl)-2-trimethylsilyfuran

A mixture of 4-(1hydroxytridecyl)-2-trimethylsilyfuran (318.5 mg, 0.9mmol), sodium hydride (60% dispersion in oil; 150 mg, 3.8 mmol) andiodomethane (0.29 ml, 4.7 mmol) in tetrahydrofuran (7 ml) was refluxedfor 16 hours. On cooling, the mixture was diluted with ethyl ether (20ml), quenched with methanol (2 ml) and washed with water. Evaporation ofthe dried (magnesium sulfate) organic phase gave a deep yellow oil,identified as 4-(1-methoxytridecyl)-2-trimethylsilylfuran.

¹ H NMR (CDCl₃): 0.32 (s, 9H), 0.94 (t, 3H, J=7.1 Hz), 1.31 (broad s,20H), 1.65 (m, 1H), 1.85 (m, 1H), 3.28 (s, 1H), 4.14 (t, 1H, J=10 Hz);6.63 (s, 1H) and 7.58 (s, 1H). The product was used directly in the nextstage without further purification.

4-(1-Methoxytridecyl)-5-hydroxy-2(5H)-furanone

A mixture of 4-(1-methoxytridecyl)-2-trimethylsilylfuran (280 mg, 0.8mmol) and Rose Bengal (5 mg) in tetrahydrofuran (7 ml) was exposed tosinglet oxygen for 5 hours at -78 degrees. The residue, after solventremoval, was flash chromatographed on silica using 60% ethylether/petroleum ether. Fractions with R_(f) of about 0.21 on evaporationafforded the 4-(1-methoxytridecyl)-5-hydroxy-2(5H) -furanone as acolorless prism: mp 53-4 degrees.

¹ H NMR (CDCl₃): 0.99 (t, 3H, J=8.3 Hz), 1.28 (broad s, 20H), 1.75 (m,2H), 3.40 (s, 3H), 3.41 (s, 3H), 4.10 (m, 1H), 4.30 (br, 1H), 6.04 (s,1H), 6.05 (s, 1H), 6.08 (s, 1H), and 6.19 (s, 1H).

¹³ C NMR (CDCl₃): 14.2, 22.7, 25.0, 25.1, 29.4, 29.5, 29.5, 29.6, 29.7,29.9, 32.0, 32.9, 33.8, 57.6, 57.9, 97.1, 97.8, 118.5, 119.7 and 168.6.

MS m/e: exact mass cald for C₁₈ H₃₃ O₄ (M+H)⁺ 313.2379, found 313.2381.

4-[1-(4-Phenylbutanoyloxy)tridecyl]2-trimethylsilylfuran

tert-Butyl lithium (a 1.7 M solution in pentane; 0.47 ml, 0.79 mmol) wasadded dropwise to a solution of4-(1-hydroxytridecyl)-2-trimethylsilylfuran (256.4 mg, 0.76 mmol),prepared as in Example 38, in tetrahydrofuran (5 ml) at -78 degreesunder argon. After 10 minutes, a solution of 4-phenylbutyryl chloride(145 mg, 0.79 mmol) was added. Stirring was continued at roomtemperature for 2 days and the mixture was quenched with water.Extraction and evaporation of the dried (magnesium sulphate) extractsgave an oil, which was purified by preparative thin-layer chromatography(20×20 cm, 1000 micron silica plate; developed with 10% ethylether/hexane) The title ester was obtained as a light yellow oil.

¹ H NMR (CDCl₃): 0.28 (s, 9H), 0.91 (t, 3H, J=7.0 Hz), 1.28 (m, 20H),1.85 (m, 2H), 1.97 (p, 2H, J=7.7 Hz), 2.35 (t, 2H, J=7.4 Hz), 2.65 (t,2H, J=7.8 Hz), 5.82 (t, 1H, J=6.9 Hz), 6.61 (s, 1H), 7.25 (m, 2H) and7.62 (s, 1H).

MS m/e (% abundance 485 (M⁺, 7) 339 (28), 321 (32), 170 (12), 154 (19),153 (18), 147 (84), 91 (46) and 73 (100).

4[1-(4-Phenylbutanoyloxy)tridecyl]-5-hydroxy-2(5H)-furanone

A mixture of 4-[1-(4-phenylbutanolyoxy)tridecyl]-2-trimethylsilylfuran(203 mg, 0.42 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (7 ml) wasexposed to singlet oxygen at -78 degrees for 100 minutes. The residue,after solvent removal, was purified by preparative TLC (20x20 cm, 500micron silica plate; developed with 60% ethyl ether/hexane). The titlefuranone was isolated as a colorless oil.

¹ H NMR (CDCl₃): 0.93 (t, 3H, J=6.4 Hz), 1.30 (brs, 20H), 1.95 (br, 2H),2.03 (p, 2H, J=7.5 Hz), 2.43 (t, 2H, J=7.3 Hz), 2.71 (t, 2H, J=7.4 Hz),5.45 (br, 1H), 5.99 (brs, 1H), 6.05 (brs, 1H), 5.25 (br, 1H), 6.20 (br,1H) and 7.30 (m, 5H).

¹³ C NMR (CDCl₃): 14.1, 22.7, 25.0, 26.2, 29.1, 29.3, 29.5, 29.6, 31.9,33.2, 33.4, 35.0, 69.0, 69.6, 98.0, 118.5, 119.1, 126.2, 128.4, 140.9,167.2, 169.7 and 173.6.

MS m/e: exact mass Calculated for C₂₇ H₄₄ NO₅ (M+NH₄))⁺ 462.3219, found462.3220.

4-[1-(3-Phenopropanoyloxy(tridecyl]-2-trimethylsilylfuran

tert-Butyl lithium (a 1.7 M solution in pentane; 0.25 ml, 0.42 mmol) wasadded dropwise to a solution of4-(1-hydroxytridecyl)-2-trimethylsilylfuran (118 mg, 0.35 mmol) intetrahydrofuran (6 ml) at -78 degrees under argon. After 25 minutes, asolution of hydrocinnamoyl chloride (62.2 microliter, 0.42 mmol) intetrahydrofuran (1/2ml) was added. Stirring was continued at roomtemperature for 7 hours and quenched with water. Extraction (ethylether) and evaporation of the dried (magnesium sulphate) extracts gavean oil, which was purified by preparative TLC (20×20 cm, 500 micron,silica plate; developed with 60% ethyl ether/hexane). The title esterwas obtained as a colorless oil.

1H NMR (CDCl₃): 0.27 (s, 9H), 0.93 (t, 3H), 1.27 (brs, 20H), 1.85 (m,2H), 2.65 (t, 2H, J=6.9 Hz), 2.96 (2H, t, J=6.9 Hz), 5.80 (t, 1H, J=7.5Hz), 6.57 (s, 1H), 7.17-7.32 (m, 5H) and 7.57 (s, 1H).

MS m/e (%abundance) 456 (M⁺, 8) 338 (30), 321 (15), 247 (5), 193 (9),153 (17), 91 (56) and 73 (100).

4-[1-(3-Phenylpropanoyloxy)tridecyl]-5-hydroxy-2(5H)-furanone

A mixture of 4-[1-3-phenylpropanoyloxy)tridecyl]-2-trimethylsilylfuran(70 mg, 0.15 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (7 ml) wasexposed to singlet oxygen at -78 degrees for 80 minutes. The residue,after solvent removal, was purified by preparative TLC (20×20 cm, 500usilica plate; developed with 60% ethyl ether/hexane). The title furanonewas isolated as a light yellow oil.

¹ H NMR (mixture of diasteriomers) (CDCl₃): 0.87 (t, 3H, J=6.9 Hz), 1.26(brs, 20H), 1.72 (m, 2H), 2.73 (brt, 2H), 2.97 (t, 2H, J=7.2 Hz), 4.77(br, 1H), 5.30 (brt, 1H), 5.48 (brt, 1H), 5.65 (s, 1H), 5.85 (s, 1H),5.90 (s, 1H), 5.95 (s, 1H) and 7.25 (m, 5H).

¹³ C NMR (mixture of diasteriomers) (CDCl₃): 14.1, 22.7, 24.8, 25.9,28.9, 29.1, 29.3, 29.5, 30.6, 30.8, 31.7, 31.8, 31.9, 32.7, 32.9, 33.1,35.3, 35.4, 35.6, 53.3, 69.7, 97.9, 118.5, 126.7, 128.2, 128.6, 139.8,166.8 and 169.7.

MS m/®: exact mass calculated for C₂₆ H₄₂ NO₅ (M+NH₄) 48.3062, found448.3052.

4-[1-(Phenylacetoxy)tridecyl]-2-trimethylsilylfuran

tert-Butyl lithium (a 1.7 M solution in pentane; 0.29 ml, 0.49 mmol) wasadded dropwise to a solution of4-(1-hydroxytridecyl)-2-trimethylsilylfuran (138.2 mg, 0.41 mmol) intetrahydrofuran (7 ml) at -78 degrees under argon. After 5 minutes, asolution of phenylacetyl chloride (65 microliter, 0.49 mmol) intetrahydrofuran (1/2ml) was added. Stirring was continued at roomtemperature for 16 hours and quenched with water. Extraction (ethylether) and evaporation of the dried (magnesium sulphate) extracts gavean oil, which was purified by preparative TLC (20×20 cm, 500 micronsilica plate; developed with 10% ethyl ether/hexane). The title esterwas obtained as a pale yellow oil.

¹ H NMR (CDCl₃): 0.25 (s, 9H), 0.89 (t, 3H, J=7.0 Hz), 1.27 (brs, 20H),1.85 (m, 2H), 3.75 (dd, 2H), 5.80 (m, 1H), 6.52 (2s, 2H), 7.20 (m, 5H),7.52 (s, 1H) and 7.54 (s, 1H).

MS m/e (% abundance) 456 (M⁺, 8), 338 (30), 321 (15), 247 (5), 193 (9),153 (17), 91 (56) and 73 (100).

4-[1-(phenylacetoxy)tridecyl]-5-hydroxy-2(5H)-furanone

A mixture of 4-[1-(phenylacetoxy)tridecyl]-2-trimethylsilylfuran (60 mg,0.13 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (5 ml) was exposedto singlet oxygen at -78 degrees for 2 hours. The residue, after solventremoval, was purified by preparative TLC (20×20 cm, 500u silica plate;developed with 60% ethyl ether/hexane). The title furanone was isolatedas a yellow oil.

¹ H NMR (mixture of diasteriomers) (CDCl₃): 0.91 (t, 3H, J=6.3 Hz), 1.28(brs, 20H), 1.85 (m, 2H), 3.65 (brs, 2H), 5.40-6.20 (m, 4H) and 7.40 (m,5H).

¹³ C NMR (mixture of diasteriomers) (CDCl₃) 14.1, 22.7, 24.5, 24.7,24.9, 28.8, 29.1, 29.3, 29.5, 29.6, 31.9, 32.9 33.1, 33.2, 41.4, 43.6,48.5, 53.4, 69.5, 70.0, 70.1, 97.3, 97.7, 97.8, 118.4, 119.2, 126.0,126.1, 126.3, 126.9, 127.1, 127.2, 127.5, 127.6, 128.3, 128.5, 128.7,128.8, 129.0, 129.2 129.4, 129.5, 129.8, 129.9, 130.0, 131.3, 166.7,169.5 and 171.6.

MS m/e: exact mass calculated for C₂₅ H₄₀ NO₅ (M+NH₄)⁺ 434.2906, found434.2914.

4-[1-(Cyclohexanoyloxy)tridecyl]-2-trimethylsilylfuran

tert-Butyl lithium (a 1.7 M solution in pentane; 0.33 ml, 0.55 mmol) wasadded dropwise to a solution of4-(1-hydroxytridecyl)-2-trimethylsilylfuran (170 mg, 0.50 mmol) intetrahydrofuran (5 ml) at 0 degrees under argon. After 10 minutes,cyclohexanecarboxylic acid chloride (74 microliter, 0.55 mmol) wasadded. The mixture was stirred at room temperature for 15 hours andquenched with water. Extraction and evaporation of the dried (magnesiumsulphate) extracts gave an oil, which was purified by preparative TLC(20×20 cm, 1000u silica plate; developed with 5% ethyl ether/hexane).The title ester was obtained as a pale yellow oil.

¹ H NMR (CDCl₃): 0.23 (s, 9H), 0.94 (t, 3H, J=6.9 Hz), 1.31 (br, 20H),1.21 (m, 12H), 2.35 (tt, 1H, J=11.3 Hz, 3.7 Hz), 5.82 (t, 1H, J=7.5 Hz),6.61 (s, 1H), and 7.62 (s, 1H).

MS m/e (% abundance 448 (M⁺, 12), 339 (18), 338 (67), 337 (20), 185(12), 170 (10), 154 (13), 153 (13), 111 (33), 84 (11), 83 (100) and 73(71).

4-[1-(Cyclohexanoyloxy)tridecyl]-5-hydroxy-2(5H)-furanone

A mixture of 4-[1-(cyclohexanoyloxy)tridecyl)-2-trimethylsilylfuran (70mg, 0.16 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (6 ml) wasexposed to singlet oxygen at -78 degrees for 2 hours. The residue, aftersolvent removal, was purified by preparative TLC (20×20 cm, 1000u silicaplate; developed with 60% ethyl ether/hexane). The title furanone wasobtained as a colorless oil.

¹ H NMR (CDCl₃) 0.91 (t, 3H, J=6.8 Hz), 1.29 (m, 6H), 1.70-2.00 (m, 6H),2.40 (m, 1H), 5.45 (br, 2H), 5.98 (br, 1H) and 6.05 (br, 1H).

¹³ C NMR (CDCl₃): 14.1, 22.7, 25.1, 25.3, 25.6, 28.8, 28.9, 29.2, 29.4,29.5, 29.7, 31.9, 33.3, 43.1, 68.7, 69.3, 98.1, 118.3, 119.0 and 167.6.

MS m/e: exact mass calculated for C₂₄ H₄₁ O₅ (M+H)⁺ 409.2953, found409.2971.

4-[1-(Dodecanoyloxy)tridecyl]2-trimethylsilylfuran

tert-Butyl lithium (a 1.7 M solution in pentane; 0.21 ml, 0.36 mmol) wasadded dropwise to a solution of4-(1-hydroxytridecyl)-2-trimethylsilylfuran (124.5 mg, 0.37 mmol) intetrahydrofuran (5 ml) at 0 degrees under argon. After 5 minutes, thecooling bath was removed and lauroyl chloride (88 microliter) was added.The mixture was stirred at room temperature for 16 hours and quenchedwith water. Extraction (ethyl ether) and evaporation of the dried(magnesium sulphate) extracts gave an oil, which was purified bypreparative TLC (20×20 cm, 1000u silica plate; developed with 5% ethylether/hexane). The title ester was obtained as a colorless oil.

¹ H NMR (CDCl₃): 0.23 (s, 9H), 0.88 (t, 3H, J=6.9 Hz) , 1.25 (brs, 36H),1.57-1.92 (m, 2H), 2.29 (t, 2H, J=7.2 Hz), 5.77 (t, 1H, J=7.5 Hz), 6.57(s, 1H) and 7.57 (s, 1H).

MS m/e (% abundance) 520 (M⁺, 9), 338 (45), 320 (18), 257 (10), 183(16), 170 (10), 154 (25), 73 (100).

4-[1-(Dodecanoyloxy)tridecyl]-5-hydroxy-2(5H)-furanone

A mixture of 4-[1-dodecanoyloxy)tridecyl]-2-trimethylsilylfuran (55 mg,0.11 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (7 ml) was exposedto singlet oxygen at -78 degrees for 2 hours. The residue, after solventremoval, was purified by preparative TLC (20×20 cm, 500u silica plate;developed with 60% ether/hexane). The title furanone was obtained as acolorless oil.

¹ H NMR (CDCl₃): 0.92 (t, 6H, J=6.4 Hz), 1.29 (brs, 38H), 1.60-1.90 (m,2H), 2.40 (t, 2H, J=7.4 Hz), 5.40 (br, 1H) and 6.02 (br, 2H).

¹³ C NMR (mixture of diasteriomers) (CDCl₃): 14.0, 14.1 15.2, 22.7,24.7, 24.9, 25.0, 25.4, 25.6, 27.9, 28.1, 28.2, 28.3, 28.5, 28.6, 28.7,28.8, 28.9, 29.1, 29.3, 29.5, 29.6, 30.0, 30.2, 30.4, 30.5, 31.9, 33.1,34.2, 34.3, 53.4, 65.9, 68.0, 69.3, 69.4, 69.5, 98.0, 118.3, 167.0,170.0 and 173.5.

MS m/e: exact mass calculated for C₂₉ H₅₃ O₅ (M+H)⁺ 481.3893, found481.3895.

4-[1-(Methylcarbamoyl)tridecyl]-2-trimethylsilylfuran

tert-Butyl lithium (a 1.7 M solution in pentane; 0.21 ml, 0.36 mmol) wasadded dropwise to a solution of4-(1-hydroxytridecyl)-2-trimethylsilylfuran (110 mg, 0.33 mmol) intetrahydrofuran (5 ml) at 0 degrees under argon. After 10 minutes, asolution of methyl isocyanate (21 microliter, 0.36 mmol) intetrahydrofuran (1/2ml) was added. Stirring was continued at roomtemperature for 2 days and the mixture was quenched with water.Extraction (ethyl ether) and evaporation of the dried (magnesiumsulphate) extracts gave an oil which was purified by preparative TLC(20×20 cm, 1000u silica plate; developed with 20% ethyl ether/hexane).The title carbamate was obtained as a yellow oil.

¹ H NMR (CDCl₃): 0.27 (s, 9H), 0.91 (t, 3H, J=6.9 Hz), 1.28 (brs, 20H),1.85 (m, 2H), 2.81 (d, 3H, J=4.9 Hz), 4.60 (br, 1H), 5.70 (t, 1H, J=7.5Hz), 6.61 (s, 1H) and 7.62 (s, 1H).

MS m/e (% abundance) 395 (M⁺, 3), 339 (19), 338 (71), 320 (16), 183(17), 169 (15), 154 (25), 132 (11), 75 (25) and 73 (100).

4-[1-(Methylcarbamoyl)tridecyl]-5-hydroxy-2(5H)-furanone

A mixture of 4-[1-(methylcarbamoyl)tridecyl]-2-trimethylsilylfuran (12.5mg, 0.03 mmol) and Rose Bengal (2 mg) in tetrahydrofuran (5 ml) wasexposed to singlet oxygen at -78 degrees for 80 minutes. The residue,after solvent removal, was purified by preparative TLC (20×20 cm, 250usilica plate; developed with 70% ethyl ether/hexane). The title furanonewas obtained as a pale yellow oil.

¹ H NMR (mixture of diasteriomers) (CDCl₃): 0.91 (t, 3H, J=6.8 Hz), 1.29(brs, 20H), 1.80 (m, 2H), 2.83 (d, 3H, J=4.9 Hz), 2.90 (d, 3H, J=4.9Hz), 4.80 (br, 1H), 4.95 (bd, 1H), 5.25 (brt, 1H), 5.45 (brt, 1H), 6.01(brs, 1H) and 6.04 (brs, 1H).

¹³ C NMR (mixture of diasteriomers) (CDCl₃) 14.1, 22.7, 25.1, 27.6,29.2, 29.4, 29.5, 29.6, 31.9, 33.2, 33.7, 69.7, 69.9, 97.9, 98.5, 118.4,118.9, 156.7, 168.4 and 169.9.

MS m/e exact mass calculated for C₁₉ H₃₃ NO₅ (M+NH₄)⁺ 373.2702, found373.2711.

4-[1-((R)-(+)-a-Methylbenzylcarbamoyl)tridecyl]-2-trimethylsilylfuran

tert-Butyl lithium (a 1.7 M solution in pentane; 0.59 ml, 1.0 mmol) wasadded dropwise to a solution of4-(1-hydroxytridecyl)-2-trimethylsilylfuran (335.5 mg, 0.99 mmol) intetrahydrofuran (6 ml) at 0 degrees under argon. After 20 minutes, asolution of (R)-(+)-alpha-methylbenzyl isocyanate (146 mg, 0.99 mmol) inTHF (1/2 ml) was added. Stirring was continued for 16 hours while thecooling bath attained room temperature. The mixture was quenched withwater and extracted with ethyl ether. Evaporation of the dried(magnesium sulphate) extracts gave an oil, which was purified bypreparative TLC (20×20 cm, two 1000u silica plates; developed with 20%ethyl ether/hexane). The title carbamate was obtained as a light yellowoil.

¹ H NMR (CDCl3): 0.30 (2s, 9H), 0.92 (brt, 3H), 1.29 (brs, 28H), 1.80(br, 2H), 4.85-5.00 (2 brs, 2H), 5.68 (t, 1H, J=7.5 Hz), 6.60 (s, 1H),6.70 (s, 1H), and 7.30 (m, 5H).

MS m/e (% abundance) 503 ((M+NH₄ ⁺, 0.1), 485 (M⁺, 0.2), 442 (1), 322(33), 321 (100), 320 (4), 238 (4), 183 (5), 122 (8) and 6 (4).

4-[1-((R)-(+)-alpha-Methylbenzylcarbamoyl)tridecyl]-5-hydroxy-2-(5H)-furanone

A mixture of4-[1-((R)-(+)-alpha-methyl-benzylcarbamoyl)tridecyl]-2-trimethylsilylfuran(71 mg, 0.15 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (5 ml) wasexposed to singlet oxygen at -78 degrees for 2 hours. The residue, aftersolvent removal, was purified by preparative TLC (20×20 cm, 500u silicaplate; developed with 60% ethyl ether/hexane). The title furanone wasobtained as a pale yellow oil.

¹ H NMR (mixture of diasteriomers) (CDCl₃): 0.91 (t, 3H, J=7.0 Hz), 1.28(brs, 18H), 1.38 (d, 3H, J=7.0 Hz), 1.50 (m, 2H), 1.78 (m, 2H), 4.80(br, m, 1H), 5.26 (m, 1H), 5.38 (m, 1H), 5.98 (brs, 1H), 6.05 (brs, 1H)and 7.35 (m, 5H).

¹³ C NMR (mixture of diasteriomers) 14.1, 15.3, 17.9, 22.1, 22.3, 22.7,25.0, 29.0, 29.1, 29.3, 29.5, 29.6, 31.9, 33.2, 3.34, 33.6, 51.0, 63.8,69.8, 69.9, 97.9, 98.3, 98.4, 104.2, 118.3, 118.4, 118.8, 125.7, 125.8,125.9, 127.7, 128.8, 142.7, 155.3, 161.8, 169.8 and I69.9.

MS m/e: exact mass calculated for C₂₅ H₃₆ NO₅ (M⁺ -CH₃): 430.2593, found430.2603.

4-(1-Trichloroacetoxy)tridecyl-2-trimethylsilylfuran

tert-Butyl lithium (a 1.7 M solution in pentane; 0.32 ml, 0.54 mmol) wasadded dropwise to a solution of4-(1-hydroxytridecyl)-2-trimethylsilylfuran (151.3 mg, 0.45 mmol) intetrahydrofuran (10ml) at 0 degrees under argon. After 10 minutestrichloroacetic anhydride (98 microliter, 0.54 mmol) was added andstirring was continued at room temperature overnight. The mixture wasquenched with water and extracted with ethyl ether. Evaporation of thedried (magnesium sulphate) extracts afforded an oil, which was purifiedby preparative TLC (20×20 cm, 500u silica plate; developed with 10%ethyl ether/petroleum ether). The title ester was obtained as a paleyellow oil.

¹ H NMR (CDCl₃): 0.28 (s, 9H), 0.91 (t, 3H, J=6.0 Hz), 1.28 (brs, 20H),2.0 (m, 2H), 5.88 (t, 1H, J=7.5 Hz), 6.64 (s, 1H) and 7.70 (s, 1H).

MS m/e (% abundance) 460/462/464 ((M+NH₄)⁺, 16, 16, 5), 426 (13), 316(21), 300 (69), 299 (21) and 298 (100).

4-(1-Trichloroacetoxy)tridecyl-5-hydroxy-2(5H)-furanone

A mixture of 4-(1-trichloroacetoxy)tridecyl-2-trimethylsilylfuran (120mg, 0.25 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (5 mg) wasexposed to singlet oxygen at -78 degrees for 1/2hour. The residue, aftersolvent removal, was purified by preparative TLC (20×20 cm, 500u silicaplate; developed with 60% ethyl ether/hexane). The title furanone wasobtained as a light yellow oil.

¹ H NMR (CDCl₃): 0.92 (t, 3H, J=7.0 Hz), 1.29 (brs, 20H), 2.02 (br, 2H),5.75 (br, 1H), 6.18 (brs +s, 2H).

¹³ C NMR (CDCl₃): 14.1, 22.7, 24.6, 28.8, 29.0, 29.3, 29.4, 29.5, 29.6,29.9, 31.7, 31.9, 32.7, 74.6, 89.5, 97.6, 119.1, 161.1, 164.5 and 169.8.

MS m/e: exact mass calculated for C₁₉ H₃₃ Cl₃ NO₅ (M+NH₄)⁺ 460.1424,found 460.1403.

4-(1-Hydroxytridecyl)-2-triethylsilylfuran

Dodecylmagnesium bromide (a 1M solution in tetrahydrofuran 14.3 ml, 14.3mmol) was added dropwise to a solution of 2-triethylsilyl-4-furaldehyde(2.0 g, 9.52 mmol) in THF (20 ml) at 0 degrees C under argon. Afterstirring at room temperature for 2 hours, the mixture was quenched withdilute HCl and extracted with ethyl ether. Evaporation of the dried(magnesium sulfate) extracts gave an oil, which was purified by flashchromatography on silica using 30% ethyl ether/hexane to give the titledalcohol.

¹ H NMR (CDCl₃) 0.76 (q, 6H, J=8.0 Hz), 0.88 (t, 3H, J=6.3 Hz). 0.98 (t,9H, J=8.0 Hz), 1.25 (m, 20H) 1,62 (d, 1H, J=4.3 Hz). 1.75 (m, 2H), 4.63(dd, 1H, J=6.6 Hz, 1.9 Hz), 6.63 (s, 1H) and 7.57 (s, 1H).

EXAMPLE 4 3-(1-Chlorotridecyl)-5-trimethylsilylfuran

Triethylamine (0.55 ml, 3.95 mmol), followed by oxalyl chloride (0.34ml, 3.95 mmol) was added dropwise to a solution of3-(1-hydroxytridecyl)-5-trimethylsilylfuran (890 mg. 2.63 mmol) inanhydrous dichloromethane (10 ml) at 0 degrees. After 40 minutes, thereaction was quenched with ice water. Extraction (dichloromethane) andevaporation of the dried (magnesium sulfate) extracts gave an oil, whichwas purified by flash chromatography on silica using 5% ethylether/hexane. Fractions with R_(f) of about 0.37 on evaporation gave thetitle chloride as a pale yellow oil, solidified to a colorless solid onstorage at -20 degrees.

¹ H NMR (CDCl₃): 0.26 (s, 9H), 0.89 (t, 3H, J=6.3 Hz), 1.26 (brs, 20H),1.85-2.05 (2m, 2H), 5.87 (t, 1H, J=7.5 Hz), 6.63 (d, 1H, J=2.3 Hz) and7.66 (d, 1H, J=2.4 HZ)

MS m/e (% abundance): 321 (M⁺ -Cl, 57), 180 (14), 154 (43), 153 (16), 75(13) and 73 (100).

3-(1-Azidotridecyl)=5-trimethylsilylfuran

A mixture of 3-(1-chlorotridecyl)-5-trimethylsilylfuran (468 mg, 1.31mmol) and sodium azide (852 mg, 13.1 mmol) in dry dimethylformamide (2ml) was stirred at 60 degrees for 6 days. Most of the solvent wasevaporated under high vacuum and the residue dissolved in water.Extraction (ethyl ether) and evaporation of the dried (magnesiumsulfate) extracts gave an oil, which was flash chromatographed on silicausing 5% ethyl ether/hexane. Fractions with R_(f) of about 0.73 onevaporation gave the title azide as a very pale yellow oil.

IR neat): 2100 (br, s), 1080

¹ H NMR (CDCl₃): 0.26 (s, 9H), 0.88 (t, 3H, J=6.3 Hz), 1.25 (brs, 20H),1.75 (m, 2H), 4.33 (t, 1H, J=7.3 Hz), 6.58 (s, 1H) and 7.59 (s, 1H).

MS m/e: Exact mass calculated for C₂₀ H₃₇ N₃ O₅ 363.2705, found363.2698.

3-(1-Aminotridecyl)-5-trimethylsilylfuran

Lithium aluminum hydride (a 1M solution in tetrahydrofuran; 1.1 ml, 1.1mmol) was added dropwise to a solution of3-(1-azidotridecyl)-5-trimethylsilylfuran (334 mg, 0.92 mmol) intetrahydrofuran at room temperature. After one hour at room temperature,the excess hydride was destroyed by adding acetone slowly to the mixturewith cooling. Sodium sulfate (ca. 0.5 g) was added and the mixture wasextracted thoroughly with ethyl acetate. Evaporation of the dried(magnesium sulfate) extracts gave an oil, which was purified by flashchromatography on silica using 5% methanol/dichloromethane containing0.2% triethylamine. Fractions with R_(f) of about 0.18 on evaporationgave the title amine as a pale yellow oil.

IR (neat): 3400-3200 (br), 1080

¹ H NMR (CDCl₃): 0.29 (s, 9H), 0.92 (t, 2H, J=7.0 Hz), 1.29 (brs, 20H),1.65 (m, 2H), 1.85 (br, 2H), 3.89 (t, 1H, J=6.8 Hz), 6.64 (s, 1H) and7.55 (s, 1H).

MS m/e: Exact mass calculated for C₂₀ H₃₈ SiN (M+H)⁺ 3 336.2722, found336.2717.

3-[1-(Acetamido)tridecyl]-5-trimethylsilylfuran

Acetic anhydride (0.1 ml) was added to a solution of3-(1-aminotridecyl)-5-trimethylsilylfuran (89.8 mg, 0.27 mmol) andtriethylamine (0.1 ml) in dichloromethane (1 ml) at room temperature.Stirring was continued overnight (14 hours) while the cooling bathattained room temperature. The residue, after solvent removal, waspurified by preparative TLC (20×20 cm, 1000u; developed with 60% ethylether/hexane). The title amide was obtained as a pale yellow oil.

¹ H NMR (CDCl₃): 0.26 (s, 9H), 0.89 (t, 3H, J=7.0 Hz), 1.27 (brs, 20H),1.75 (m, 2H), 2.00 (s, 3H), 4.97 (dt, 1H, J=8.8 Hz, 7.0 Hz), 5.56 (d,1H, J=8.8 Hz), 6.55 (s, 1H) and 7.53 (s, 1H).

MS m/e: Exact mass calculated for C₂₂ H₄₁ NO₂ Si 379.2906, found379.2908.

3-[1-(Acetamido)tridecyl)1-5-hydroxy-2(5H)-furanone (Compound 29)

A mixture of 3-[1-(acetamido)tridecyl]-5-trimethylsilylfuran (81 mg,0.21 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (5 ml) was exposedto singlet oxygen at -78 degrees for 2 hours. The residue, after solventremoval, was purified by preparative TLC (20×20 cm, 1000u silica plate;developed with ethyl acetate). The title furanone was obtained ascolorless solid, mp 102-3 degrees.

¹ H NMR (CDCl₃): 0.92 (t, 3H, J=7.1 Hz), 1.29 (brs, 20H), 1.75 (m, 2H),2.07 (brs, 3H), 4.55 (m, 1H), 4.85 (m, 1H), 5.95 (brs, 1H), 6.05 (br,1H), 6.15 (br, 1H), 6.30 (d, 1H) and 7.0 (br, 1H).

¹³ C NMR (CDCl₃): 14.1, 22.7, 22.8, 25.8, 29.1, 29.3, 29.5, 29.6, 31.9,33.5, 47.8, 99.2, 117.9, 170.2, 170.3 and 171.3.

MS m/e: Exact mass calculated for C₁₉ H₃₄ NO₄ (M+H)⁺ 340.2487, found340.2476.

3-[1-(Trifluoroacetamido)tridecyl]-5-trimethylsilylfuran

Trifluoroacetic anhydride (0.05 ml) was added to a solution of3-(1-aminotridecyl)-5-trimethylsilylfuran (80.7 mg, 0.24 mmol) andtriethylamine (0.1 ml) in dichloromethane (1 ml) at room temperature.Stirring was continued overnight (14 hours) while the cooling bathattained room temperature. The residue, after solvent removal, waspurified by preparative TLC (20×20 cm, 1000u silica plate; developedwith 10% ethyl ether/hexane). The title amide was obtained as a paleyellow oil.

¹ H NMR (CDCl₃): 0.27 (s, 9H), 0.89 (t, 3H, J=7.0 Hz), 1.26 (brs, 20H),1.85 (m, 2H), 4.98 (dt, 1H, J=8.3 Hz, 7.5 Hz), 6.25 (d, 1H, J=8.3 Hz),6.54 (s, 1H) and 7.58 (s, 1H).

MS m/e: Exact mass calculated for C₂₂ H₃₈ NO₂ SiF₃ (M+) 433.2624, found433.2624.

4-1-Trifluoroacetamido)tridecyl]-5-hydroxy-2(5H)-furanone (Compound 30)

A mixture of 3-[1-trifluoroacetamido)tridecyl]-5-trimethylsilylfuran (60mg, 0.14 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (5 ml) wasexposed to singlet oxygen at -78 degrees for 2 hours. The residue, aftersolvent removal, was purified by preparative TLC (20×20 cm, 1000u; 60%ethyl ether/hexane). The title furanone was obtained as a colorlesssolid, mp 138-9 degrees.

¹ H NMR (CD₃ OD): 0.89 (t, 3H, J=7 Hz), 1.29 (brs, 20H), 1.75-1.95 (m,2H), 4.80-4.90 (br, 3H), 6.0 (br, 1H) and 6.15 brs, 1H).

¹³ C NMR (CDCl₃): 14.4, 23.8, 26.9, 30.0, 30.4, 30.5, 30.6, 30.8, 33.1,100.2, 100.4, 100.6, 115.6, 119.3, 119.4, 119.5, 119.7, 119.8, 119.9,158.6, 159.1, 169.6 and 172.3.

MS m/e: Exact mass calculated for C₁₉ H₃₁ NF₃ O₄ (M+H) 394.2205, found394.2195.

3-[1-Methylsulfonamido)tridecyl]-5-trimethylsilylfuran

Methanesulfonyl chloride (37 ul, 0.48 mmol) was added to a solution of3-(1-aminotridecyl)-5-trimethylsilylfuran (134.6 mg, 0.4 mmol) andtriethylamine (67 ul, 0.4S mmol) in dichloromethane (2 ml) at 0 degrees.Stirring continued overnight (14 hours) while the cooling bath attainedroom temperature. The reaction mixture was quenched with water.Extraction (ethyl ether) and evaporation of the dried (magnesiumsulfate) extracts gave an oil, which was purified by flashchromatography on silica using 10% ethyl ether/hexane. Fractions withR_(f) of about 0.07 on evaporation gave the title sulfonamide as a paleyellow oil.

¹ H NMR (CDCl₃): 0.27 (s, 9H), 0.89 (t, 3H, J =6.4 Hz), 1.26 (brs, 20H),1.75 (m, 2H), 2.77 (s, 3H), 4.45 (dt+d, 2H), 6.56 (1H) and 7.59 (s, 1H).

MS m/e: Exact mass calculated for C₂₁ H₄₁ NSiSO₃ (M⁺) 415.2581, found415.2576.

4-[1-(Methylsulfonamido)tridecyl]-5-hydroxy-(5H)-furanone

A mixture of 3-[1-(methylsulfonamido)tridecyl]-5-trimethylsilylfuran (64mg, 0.189 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (6 ml) wasexposed to singlet oxygen at -78 degrees for 2 hours. The residue, aftersolvent removal, was purified by preparative TLC (20×20 cm, 1000u silicaplate; developed with 70% ethyl ether/hexane. The title furanone wasobtained as an off-white solid, mp 95-6 degrees.

¹ H NMR (CDCL3): 0.89 (t, 3H, J=7.0 Hz), 1.26 (brs, 20H), 1.75 (m, 2H),3.02 (s, 3H), 4.35 (m, 1H), 5.45 (brd, 1H), 5.55 (brs, 1H), 6.10 (brs,1H) and 6.22 (br, 1H).

²³ C NMR (CDCl₃) 13.9 , 22.5, 25.5, 28.9, 29.1, 29.2, 29.4, 29.9, 31.7,41.5, 97.9, 98.0, 119.5, and 170.7.

MS m/e: Exact mass calculated for C₁₈ H₃₄ SNO₅ (M⁺) 376.2157, found376.2165.

3-[1-(Methylcarbamoyl)tridecyl]-5-trimethylsilylfuran

Methyl chloroformate (30 ul, 0.39 mmol) was added to a solution of3-(1-aminotridecyl)-5-trimethylsilylfuran (109.2 mg, 0.32 mmol) andtriethylamine (54 ul, 0.39 mmol) in dichloromethane (2 ml) at 0 degrees.Stirring was continued overnight (14 hours) while the cooling bathattained room temperature. The residue, after solvent removal, waspurified by preparative TLC (20×20 cm, 1000u silica plate; developedwith 10% ethyl ether/hexane). The title carbamate was obtained as a paleyellow oil.

¹ H NMR (CDCl₃): 0.27 (s, 9H), 0.90 (t, 3H, J=7.0 Hz), 1.27 (brs, 20H),1.75 (m, 2H), 3.70 (s, 3H), 4.70 (bt +bd, 2H) 6.54 (5.1H) and 7.53 (s,1H).

MS m/e: Exact mass calculated for C₂₂ H₄₁ SiNO₃ 395.2855, found395.2842.

4-1-(Methylcarbamoyl)tridecyl]-5-hydroxy-2(5H)-furanone

A mixture of 3-[1-(methylcarbamoyl)tridecyl]-5-trimethylsilylfuran (42mg, 0.11 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (6 ml) wasexposed to singlet oxygen at -78 degrees for 2 hours. The residue, aftersolvent removal, was purified by preparative TLC (20×20 cm, 1000u;developed with 70% ethyl ether/hexane). The title furanone was obtainedas a colorless oil, which solidified on storage, mp 77-8 degrees.

¹ H NMR (CDCl₃): 0.89 (t, 3H, J=7.0 Hz), 1.26 (brs, 20H), 1.75 (brm,2H), 3.69 (brs, 3H), 4.50 (br, 1H), 5.35 (br, 1H), 5.99 (brs, 1H), 6.05(br, 1H) and 6.15 (br, 1H).

¹³ C NMR (CDCl₃): 14.1, 22.7, 25.7, 28.9, 29.1, 29.3, 29.5, 29.6, 30.0,31.9, 33.7, 48.4, 49.1, 52.8, 52.9, 98.1, 98.6, 106.1, 118.2, 118.8,157.0, 167.8, 170.1 and 170.4.

MS m/e: Exact mass calculated for C₁₉ H₃₄ NO₅ (M+H)⁺ 356.2436, found356.2431.

3-1(-aminotridecyl)-5-trimethylsilylfuran is reacted with methylmethylphosphonochloridate to give 3-[1-(3-PN(OCH₃(CH₃)O-tridecyl]-5-trimethylsilylfuran. Oxidizing with singlet oxygengives 4-[1-(3-PN(OCH₃)(CH₃)O-tridecyl]-5-hydroxy-2(5H)-furanone.

3-[(N-methylureido)tridecyl]-5-Trimethylsilylfuran

A solution of methylisocyanate (23ul, 0.38 mmol) in dichloromethane (0.5ml) was added to a solution of 3-(1-aminotridecyl)-5-trimethylsilylfuran(85.5 mg, 0.25 mmol) and triethylamine (53 microliter, 0.3 mmol) indichloromethane (2 ml) at room temperature. Stirring was continued fortwo days and the reaction mixture was quenched with water. Extraction(dichloromethane) and evaporation of the dried (magnesium sulfate)extracts gave an oil, which was purified by preparative TLC (20×20 CM,1000ul; developed with 40% ethyl acetate/hexane) to give the titled ureaas acetate/hexane) to give the titled urea as a colorless oil.

¹ H NMR (CDCl₃): 0.24 (s, 9H), 0.88 (t, 3H, J=7.0 Hz), 1.26 (s, 20H),1.70 (m, 2H), 2.72 (d, 3H, J=4.8 Hz), 4.65 (m, 2H), 4 80 (m, 1H), 6.53(s, 1H) and 7.49 (s, 1H).

4-[-1-(N-methylureido)tridecyl]-5-hydroxy-2(5H)-furanone (Compound 32)

A mixture of 3-[1-(N-methylureido)tridecyl]-5-trimethylsilylfuran (53mg. 0.14 mmol) and Rose Bengal (Ca., 2 mg) in tetrahydrofuran (5 ml) wasexposed to singlet oxygen at 0 degrees for 1.5 hours. The residue, aftersolvent removal, was purified by preparative TLC (20×20 cm, 1000u;developed with 60% ethyl acetate/hexane) to give the titled furanone asa colorless oil.

¹ H NMR (CDCl₃): 0.89 (t, 3H, J=6.8 Hz), 1.27 (brs, 20H), 1.75 (br, 2H),2.74 (d, 3H, J=4.7 Hz), 4.45 (br, 1H), 5.28 (br, 1H), 5.65 (brs, 2H),5.98 (brs, 1H) and 6.10 (brs, 1H).

4-[(-Glutarylamido)tridecyl]-2-triethylsilylfuran

A mixture of 4-(1-aminotridecyl)-2-triethylsilylfuran (250 mg, 0.66mmol) and glutaric anhydride (150 mg, 1.32 mmol) in dichloromethane wasstirred at room temperature for 2 days. The mixture was quenched withdilute hydrochloric acid and was extracted thoroughly with ethylacetate. Evaporation of the dried (magnesium sulfate) extracts gave aresidue which was purified by a silica column using 5%methanol/dichloromethane to give the titled amide as a colorless solid.

¹ H NMR (CDCl₃): 0.75 (q, 6H, J=8.0 Hz), .088 (t, 3H, J=6.5 Hz), 0.99(t, 9H, J=8.0 Hz), 1.24 (m, 20H), 1.70 (p, 2H, J=7.3 Hz), 1.97 (m, 2H),2.28 (t, 2H, J=23 Hz), 2.41 (t, 2H, J=7.3 Hz), 4.97 (q, 1H, J=8.2 Hz),5.65 (d, 1H, J=8.2 Hz), 6.50 (s, 1H) and 7.50 (s, 1H).

¹³ C NMR (CDCL3): 3.15, 7.30, 14.1, 20.8, 22.7, 26.0, 29.3, 29.5, 29.6,31.9, 33.0, 35.3, 35.4, 45.3, 119.7, 126.3, 143 4, 159.5, 171.5 and177.8.

HRMS exact mass calculated for C₂₈ H₅₁ NO₄ Si (M⁺) 493.3587, found493.3577.

4-[(1-Glutarylamido)tridecyl]-5-hydroxy-2(5H)-furanone

A mixture of 4-(1-glutarylamido)tridecyl]-2-triethylsilylfuran (222.5mg, 0.45 mmol), water (a few drops) and Rose Bengal (5 mg) was exposedto singlet oxygen at 0 degrees for 1.5 hours. The residue, after solventremoval, was purified by a silica column using 10% methanol/chloroformto give the titled furanone as a colorless solid.

¹ H NMR (CD₃ OD): 0.79 (t, 3H, J=6.5 Hz), 1.18 (m, 20H), 1.50 (m, 2H),1.80 (t, 2H, J=7.0 Hz), 2.23 (t, 4H, J=7.0 Hz), 4.60 (m, 1H), 4.73 (m,1H), 5.82 (brs, 1H), 5.88 (brs, 1H), 5.99 (brs, 1H), 8.20 (m, 1H) and8.30 (m, 1H).

¹³ C NMR (CD₃ OD): 14.4, 22.2, 23.7, 26.9, 30.1, 30.5, 30 7, 30.8, 33.0,34.0, 35.8, 99.8, 100.3, 118.1, 118.7, 172.1, 172.6, 172.7, 172.8, 175.1and 176.7.

HRMS exact mass calculated for C₂₂ H₃₈ NO₆ (M+H) 412.2696, found412.2696.

4-(1-Azidotridecyl)-2-triethylsilylfuran

A solution of diphenylphosphonyl azide (143 mg, 0.52 mmol in THF (2 ml)was added over a period of 15 minutes to a solution of4-(1-hydroxytridecyl)-2-triethylsilylfuran (200 mg, 0.52 mmol),triphenylphosphine (140 mg, 0.52 mmol) and diethyl azidocarboxylate (90mg, 0.52 mmol) in THF (10 ml) at room temperature. After stirring for 2days, the mixture was evaporated in the presence of a minimum amount ofsilica gel. The residue was purified by flash chromatography on silicausing 5% ethyl ether/hexane to give the titled azide.

¹ H NMR (CDCl₃) 0.77 (q, 6H, J=0.8 Hz), 0.88 (t, 3H, J =6.4 Hz), 0.98(t, 9H, J=8.0 Hz), 1.25 (m, 20H), 1.75 (m, 2H), 4.33 (t, 1H, J=7.5 Hz),6.60 (s, 1H) and 7.61 (s, 1H).

4-(1-Aminotridecyl)-2-triethylsilylfuran

A solution of lithium aluminum hydride (a 1.0 M solution in THF; 4.22ml, 4.22 mmol) was added slowly to a solution of4-(1-azidotridecyl)-2-triethylsilylfuran (1.55 g, 3.84 mmol) at 0degrees C under argon. After stirring at room temperature for 2 hours,the mixture was cooled to 0 degrees C. and quenched with 2M sodiumhydroxide. Anhydrous sodium sulfate was added to coagulate the aluminumsalt and the mixture was extracted thoroughly with ethyl acetate.Evaporation of the dried (magnesium sulfate) extracts gave an oil, whichwas purified by flash chromatography on silica using 5%methanol/dichloromethane to give the titled amine.

¹ H NMR (CDCl₃) 0.76 (q, 6H, J=8.0 Hz), 0.88 (t, 3H, J=6.5 Hz), 0.98 (t,9H, J=8.0 Hz), 1.25 (m, 20H), 1.80 (m, 2H), 3.85 (t, 1H, J=6.8 Hz), 6.60(s, 1H) and 7.50 (s, 1H).

EXAMPLE 5 Methyl 3-(2-trimethylsilyl-4-furyl)propen-2-oate

A mixture of methyl(triphenylphosphoranylidene) acetate (994 mg, 2.97mmol) and 2-trimethylsilyl-4-furaldehyde (384 mg, 2.29 mmol) intetrahydrofuran (10ml) was stirred at room temperature for 48 hours. Thereaction mixture was evaporated with a minimum amount of silica and theresidue was flash chromatographed on silica using 5% ethylether/petroleum ether. Fraction with R_(f) of about 0.16 on evaporationafforded the title ester as a pale yellow oil.

¹ H NMR (CDCl₃): 0.39 (s, 9H), 3.79 (s, 3H), 6.15 (d, 1H, J=15.9 Hz),6.79 (s, 1H), 7.60 (d, 1H, J=15.9 Hz) and 7.83 (s,

¹³ C NMR (CDCl₃): -2.0, 51.3, 116.7, 122.5, 134.9, 148.6, 162.8 and167.4.

MS m/®: Exact mass calculated for C₁₁ H₁₆ O₃ Si (M⁺): 224.0868, found224.0875.

Methyl 3-(2-trimethylsilyl-4-furyl)propionate

A solution of methyl-1-(2-trimethylsilyl-4-furyl)-propen-2-oate (107.7mg, 0.48 mmol) in ethyl ether (5 ml) was hydrogenated over platinum (IV)oxide (ca. 10 mg ) at room temperature for 14 hours. The mixture wasfiltered through celite and the filtrate on evaporation gave the desiredester, which was used directly in the next step.

¹ H NMR (CDCl₃): 0.24 (s, 9H), 2.57 (t, 2H, J=6.7 Hz), 2.76 (t, 2H,J=6.7 Hz), 3.69 (s, 3H), 6.49 (s, 1H) and 7.43 (s, 1H).

¹³ C NMR (CDCl₃): -1.8 , 20.0, 34.6, 51.4, 120.7, 123.3, 143.1, 160.6and 173.2.

MS m/e Exact mass calculated for C₁₁ H₁₈ O₃ Si (M⁺): 226.1025, found226.1034.

3-(2-Trimethylsilyl-4-furyl)propan-1-ol

A solution of methyl 3-(2-trimethylsilyl-4-furyl)-propionate (fromabove) in tetrahydrofuran (3 ml) was added dropwise to a suspension oflithium aluminum hydride (27 mg) in tetrahydrofuran (4 ml) at roomtemperature. After 3 hours, the mixture was quenched with ethyl acetateand extracted with ether. Evaporation of the dried (magnesium sulphate)extracts gave the title alcohol, which was used in the next step withoutpurification.

¹ H NMR (CDCl₃) 0.25 (s, 9H), 1.65 (br, 1H), 1.84 (p, 2H, J=7.3 Hz),2.52 (t, 2H, J=7.8 Hz), 3.69 (t, 2H, J=6.3 Hz), 6.51 (s, 1H) and 7.42(s, 1H).

MS m/e (% abundance): 1.98 (M⁺, 11), 154 (70), 139 (26), 101 (26), 73(79).

3-(2-Trimethylsilyl-4-furyl)propan-1-al

To a stirring mixture of pyridinium chlorochromate (3.89 g, 18.03 mmol)suspended in methylene chloride (100 ml) at 0 degrees was added3-(2-trimethylsilyl-4-furyl)propan-1-ol (1.19 g, 6.01 mmol), prepared asin Example 2, in dry methylene chloride (15 ml). This mixture wasallowed to warm to room temperature, stirred for 90 minutes, filteredand concentrated to give the desired aldehyde.

IR (CHCl₃): 3020, 1720, 1220 cm⁻¹.

¹ H NMR (CDCl₃) 9.82 (s, 1H); 7.42 (s, 1H); 6.48 (s, 1H); 2.65 to 2.85(m, 4H); 0.24 (s, 9H).

¹³ C NMR (CDCl₃): 201.8, 161.1, 143.2, 123 2, 120.7, 44.1, 17.3, -1.7.

MS m/e: calculated for C₁₀ H₁₆ O₂ Si(M⁺): 196.0919, found 196.0943.

Dimethyl-2-oxotridecylphosphonate

To a stirred solution of methyl laurate (1.5 g, 7.0 mmol) intetrahydrofuran (120 ml) at -78 degrees was added the lithium salt ofdimethylmethylphosphonate (0.901 g, 7.26 mmol; generated with n-butyllithium (5.29 ml of a 1.39 M solution in hexane). The stirring mixturewas warmed to room temperature over four hours and partitioned betweenethyl ether and 5% aqueous ammonium chloride solution. The organicportion was washed with 5% sodium bicarbonate, water, saturated sodiumchloride solution, dried over magnesium sulfate, filtered andconcentrated to give a colorless oil. Purification by flashchromatography (silica, 80% to 90% ethyl acetate/hexane) gave thedesired phosphonate ester.

IR (CHCl₃): 2920, 2850, 1710, 1250 cm⁻¹.

¹ H NMR (CDCl₃): 3.81 (s, 3H); 3.77 (s, 3H); 3.09 (d, J=22.7 Hz, 2H);2.61 (t, J=7.3 Hz, 2H); 1.51 to 1.62 (m, 2H); 1.20-1.35 (m, 16H): 0.88(t, J=6.7 Hz, 3H).

¹³ C NMR (CDCl₃): 201.9, 52.9, 52.8, 44.1, 42.0, 40.2, 31.8, 29.5, 29.2,28.9, 28.8, 23.3, 22.5, 14.0.

MS m/e: Calculated for C₁₅ H₃₁ O₄ P(M⁺): 306.1960 found 306 1963.

4-(6-Oxo-3-hexadecenyl)-2-trimethylsilylfuran

To sodium hydride (0.016 g, 0.677 mmol) under argon was addeddimethyl-2-oxotridecylphosphonate (0.207 g, 0.677 mmol) intetrahydrofuran (5 ml). The mixture was stirred for 20 minutes at roomtemperature, followed by the addition of3-(2-trimethylsilyl-4-furyl)propan-1-al (0.111 g, 0.564 mmol) intetrahydrofuran (5 ml). After stirring for five hours the reaction wasquenched with 10% aqueous hydrochloric acid and extracted with ethylether. The organic portion was washed with 5% sodium bicarbonate, water,saturated sodium chloride solution, dried over magnesium sulfate,filtered and concentrated to give an oil. Purification by flashchromatography (silica, 3% to 5% ethyl acetate/hexane) gave the desiredenone.

IR (CHCl₃): 2940, 1660, 1250 cm⁻¹.

¹ H NMR (CDCl₃): 7.41 (s, 1H); 6.77 to 6.90 (m, 1H); 6.49 (s, 1H); 6.13(d, J=16.0 Hz, 1H); 2.42 to 2.65 (m, 6H); 1.59 (t, J=7.1 Hz, 2H); 1.21to 1.35 (m, 16H); 0.89 (t, J=6.7 Hz, 2H); 0.25 (s, 9H).

¹³ C NMR (CDCl₃) 200.9, 160.8, 145.9, 143.1, 130.6, 123.6, 120.7, 40.2,32.8, 31.9, 29.6, 29.4, 29.3, 24.3, 23.3, 22.6, 14.0, -1.7.

Ms m/e: Calculated for C₂₃ H₄₀ O₂ Si(M⁺): 376.2797, found 376.2808.

4-(5-Oxo-3-hexadecenyl)-5-hydroxy-2(5H)-furanone

A stirred solution of 4-(5-oxo-3-hexadecenyl)-2-trimethylsilylfuran (47mg, 0.125 mmol) and Rose Bengal in acetone (2 ml) was flushed withoxygen and cooled to -78 degrees. The solution was subsequentlyirradiated with a 150 watt flood lamp while under constant, positivepressure of oxygen until starting material was no longer visible by TLC.The solution was warmed to room temperature, concentrated and passedthrough silica (40% ethyl acetate/hexane) to give a pale red solid. Thismaterial was further purified by recrystallization (hexane/ethyl ether)to give the desired hydroxybutenolide.

IR (CHCl₃): 3340 (broad), 2920, 1750, 1630 cm⁻¹.

¹ H NMR (CDCl₃): 6.83 (dt, J=16 Hz, J=5.8 Hz, 1H); 6.19 (d, J=16Hz, 1H);6.13 (broad s, 1H); 6.06 (s, 1H); 5.87 (s, 1H); 2.45 to 2.75 (m, 6H);1.59 (t, J=7.0 Hz, 2H); 1.15 to 1.40 (m, 16H); 0.88 (t, J=6.7 Hz, 3H).

¹³ C NMR (CDCl₃) 201.5, 171.5, 168.2, 144.4, 131.0, 117.9, 99.2, 40.5,31.8, multiple peaks from 29.0 to 29.5, 25.9, 24.1, 22.6, 14.0.

MS m/e: calculated for C₂₀ H₃₆ O₄ N(M+NH₄)⁺ : 354,2644, found 354.2658.

4-(5-Oxohexadecyl)-2-trimethylsilylfuran

To 4-(5-oxo-3-hexadecenyl)-2-trimethylsilylfuran (98 mg, 0.261 mmol),prepared as in Example 3, in ethyl acetate (2 ml) was added platinumoxide (10 mg, 0.044 mmol). This mixture was subjected to one atmosphereof hydrogen at room temperature with stirring for 21/2 hours. Thereaction mixture was filtered and concentrated to give a yellow oil.Purification by flash chromatography (silica, 3% ethyl ether/hexane)gave the desired ketone.

IR (CHCl₃): 2920, 1700 cm⁻¹.

¹ H NMR (CDCl₃): 7.39 (s, 1H); 6.48 (s, 1H); 2.27 to 2.50 (m, 6H); 1.50to 1.70 (m, 6H); 1.10 to 1.40 (m, 16H); 0.88 (t, J=6.6 Hz, 3H); 0.24 (s,9H).

¹³ C NMR (CDCl₃) 211.3, 160.4, 142.9, 124.7, 121.0, 42.8, 42.7, 31.9,29.7, 29.6, 29.4, 29.2, 24.2, 23.8, 23.5, 22.7, 14.1-1.7.

MS m/e: Calculated for C₂₃ H₄₂ O₂ Si(M⁺): 378.2954, found 378.2968.

4-(5-Oxohexadecyl)-5-hydroxy-2(5H)-furanone

A stirred solution of 4-(5-oxohexadecyl)-2-trimethylsilylfuran (71 mg,0.187 mmol) and Rose Bengal in acetone (20 ml) was flushed with oxygenand cooled to -78 degrees. The solution was subsequently irradiated witha 150 watt flood lamp while under constant positive pressure of oxygenuntil no starting material remained. The solution was warmed to roomtemperature, concentrated and filtered through silica to give a pale redsolid. Purification by flash chromatography (silica, 40% ethylacetate/hexane) gave the desired hydroxybutenolide.

IR (CHCl₃): 3360 (broad), 2920, 1740, 1705 cm⁻¹.

¹ H NMR (CDCl₃): 6.04 (d, J=5.5 Hz, 1H); 5.80 t o 5.90 (m, 2H); 2.32 to2.57 (m, 6H); 1.50 to 1.73 (m, 6H), 1.20 to 1.40 (m, 16H); 0.88 (t,J=6.7 Hz, 3H).

¹³ C NMR (CDCl₃): 212.1, 171.9, 169.7, 117.4, 99.3, 43.0, 42.0, 31.9,29.6, 29.4, 29.3, 29.2.

MS m/e: Calculated for C₂₀ H₃₄ O₄ (M⁺): 338.2457, found 338.2449.

Triethyl 1-decylphosphonoacetate

To a suspension of sodium hydride (0.321 g, 13.38 mmol) intetrahydrofuran 30 ml) at room temperature was addedtriethylphosphonoacetate (2.0 g, 8.92 mmol). After stirring for 15minutes to this mixture was added 1-bromodecane (2.17 g, 9.81 mmol) andsodium iodide (0.30 g, 2.00 mmol). After refluxing for 18 hours thereaction was quenched with 10% aqueous hydrochloric acid and extractedinto ethyl ether. The organic portion was washed with 5% sodiumbicarbonate, water, saturated sodium chloride solution, dried overmagnesium sulfate, filtered and concentrated to give a yellow oil.Purification by flash chromatography (silica, 30% to 50% ethylacetate/hexane) gave the desired phosphonate ester.

IR (CHCl₃): 3010, 2920, 1720, 1230 cm⁻¹.

¹ H NMR (CDCl₃): 4.08 to 4.26 (m, 6H); 2.86 to 2.92 (ddd, J=10.9 Hz,22.5 Hz, 3.8 Hz, 1H); 1.75 to 1.90 (m, 1H); 1.90 to 2.05 (m, 1H); 1.20to 1.40 (m, 25H); 0.88 (t, J=6.6 Hz, 3H).

¹³ C NMR (CDCl₃); 168.6, 62.1, 62.0, 61.9, 60.6, 46.2, 44.4, 31.4multiple peaks from 26.4 to 29.0, 22.1, 15.9, 15.8, 13.6, 13.5.

MS m/e: Calculated for C₁₈ H₃₈ O₅ P (MH)⁺ : 365.2457, found 365.2465.

(E) Ethyl 2-decyl-5-(2-trimethylsilyl-4-furyl)-oenten-2-oate and (Z)Ethyl 2-decyl-5-(2-trimethylsilyl-4-furyl)penten-2-oate

To sodium hydride (0.111 g, 2.78 mmol) under argon was added triethyl1-decylphosphonoacetate (0.813 g, 2.32 mmol) in tetrahydrofuran (10 ml).The mixture was stirred for 10 minutes at room temperature, followed bythe addition of 3-(2-trimethylsilyl-4-furyl)propan-1-al (0.455 g, 2.32mmol). After 10 minutes the reaction was quenched with 10% aqueoushydrochloric acid and extracted with ethyl ether. The organic portionwas washed with 5% sodium bicarbonate, water, saturated sodium chloridesolution, dried over magnesium sulfate, filtered and concentrated togive a yellow oil. Purification by preparative TLC (silica, 3% ethylacetate/hexane) afforded the desired E and Z isomers.

(Z) Ethyl 2-decyl-5-(2-trimethylsilyl-4-furyl)penten-2-oate

IR (CHCl₃): 2930, 2860, 1695, 1250 cm⁻¹.

¹ H NMR (CDCl₃): 7.24 (s, 1H); 6.75 (t, J=7.3 Hz, 1H); 6.50 (s, 1H);4.19 (q, J=7.1 Hz, 2H); 2.50 to 2.62 (m, 2H); 2.38 to 2.48 (m, 2H); 2.27(t, J=7.3, 2H); 1.20 to 1.50 (m, 19H); 0.88 (t, J=6.7 Hz, 3H); 0.25 (s,9H).

¹³ C NMR (CDCl₃) 168.1, 160.7, 143.1, 141.1, 133.3, 124.1, 60.4, 31.9,multiple peaks from 29.6 to 29.2, 26.8, 24.0, 22.7, 18.0, 14.3, 14.1,-1.7.

MS m/e: Calculated for C₂₄ H₄₂ O₃ Si(M⁺): 406.2903, found 406.2892.

(E) Ethyl 2-decyl-5-(2-trimethylsilyl-4-furyl) penten-2-oate

IR (CHCl₃): 2920, 2850, 1695, 1245 cm⁻¹.

¹ H NMR (CDCl₃): 7.41 (s, 1H); 6.50 (s, 1H); 5.85 (t, J=7.1 Hz, 1H);4.18 (q, J=7.1 Hz, 2H); 2.61 to 2.73 (m, 2H); 2.49 to 2.60 (m, 2H); 2.23(t, J=7.3 Hz, 2H); 1.15 to 1.50 (m, 19H); 0.89 (t, J=5.8 Hz, 3H); 0.26(s, 9H).

¹³ C NMR (CDCl₃): 168.2, 160.3, 143.1, 140.0, 133.0, 124.3, 121.1, 60.0,34.5, 31.9, multiple peaks from 28.7 to 29.9, 24.5, 22.7, 14.3, 14.1,-1.6.

MS m/e: calculated for C₂₄ H₄₂ O₃ Si(M⁺): 406.2903, found 406.2898.

4-(4-Carboethoxytetradecyl)-2-trimethylsilylfuran

To a stirred solution of (Z) ethyl2-decyl-5-(2-trimethylsilyl-4-furyl)penten-2-oate (99 mg, 0.244 mmol) inethyl acetate (5 ml) was added platinum oxide (28 mg, 0.122 mmol) Thismixture was subjected to one atmosphere of hydrogen for 18 hours, thenfiltered and concentrated to give an oil. Purification by flashchromatography (silica, 0% to 3% ethyl ether/hexane) gave the desiredester.

IR (CHCl₃): 2920, 2850, 1700 cm⁻¹.

¹ H NMR (CDCl₃): 7.39 (s, 1H); 6.47 (s, 1H); 4.14 (q, J=7.0 Hz, 2H);2.27 to 2.44 (m, 3H); 1.37 to 1.70 (m, 6H); 1.15 to 1.36 (m, 19H); 0.88(t, J=6.5 Hz, 3H); 0.24 (s, 9H).

¹³ C NMR (CDCl₃): 176.4, 160.4, 143.0, 124.7, 121.0, 60.0, 45.6, 32.5,32.3, 32.1, 31.9, 29.8, 29.6, 29.5, 29.3, 27.9, 27.4, 24.5, 22.7, 14.3,14.1, -1.6.

MS m/e; Calculated for C₂₄ H₄₄ O₃ Si(M⁺): 408.3060, found 408.3065.

4-(4-Carboethoxytetradecyl)-5-hydroxy-2(5H)-furanone

A stirred solution of 4-(4-carboethoxytetradecyl)-2-trimethylsilylfuran(50 mg, 0.123 mmol) and Rose Bengal in acetone (25 ml) was flushed withoxygen and cooled to -78 degrees. The solution was subsequentlyirradiated with a 150 watt flood lamp while under constant, positivepressure of oxygen until no starting material was visible by TLC. Thesolution was warmed to room temperature and concentrated to give a redoil. Purification by preparative TLC (silica, 30% ethyl acetate/hexane)gave the desired hydroxybutenolide.

IR (CHCl₃): 3340 (broad, 2920, 2825, 1720 cm⁻¹.

¹ H NMR (mixture of diastereomers), (CDCl₃): 6.01 (s, 1H); 5.84 (s, 1H);5.29 (broad s, 1H); 4.15 (q, J =7.1 Hz, 2H); 2.25 to 2.51 (m, 3H); 1.15to 1.75 (m, 25H); 0.88 (t, J =6.7 Hz, 3H).

¹³ C NMR (mixture of diastereomers), (CDCl₃): 176.6, 171.6, 169.3,117.6, 99.1, 60.5, 45.5, 32.6, 31.9, 31.7, multiple peaks between 29.3and 29.6 multiple peaks between 27.3 and 27.6, 24.5, 22.7, 14.3, 14.1.

MS m/e: Calculated for C₂₁ H₃₆ O₅ (M⁺) 368.2563, found 368.2558.

(E)(Z)-Methyl 3-(2-triethylsilyl-4-furyl)propen-2-oate) (Compound 10)

A mixture of methyl(triphenylphosphoranylidene) acetate (4.77 g, 14.3mmol) and 5-triethylsilyl-3-furaldehyde (2.0 g, 9.5 mmol) intetrahydrofuran (30 ml) was refluxed under argon for 2 days. Thereaction mixture was evaporated with a minimum amount of silica and theresidue was chromatographed on a silica column using 2.5% ethylether/hexane to give a mixture of (E),(Z)-methyl3-(2-triethylsilyl-4-furyl)propen-2-oate. (E)-isomer, R_(f) 0.19 (5%ethyl ether/hexane) and (Z)-isomer, R_(f) 0.38 (5% ethyl ether/hexane).

¹ H NMR (CDCl₃) (E)-isomer: 0.78 (q, 6H, J=8.0 Hz), 0.99 (t, 9H, J=8.0Hz), 3.78 (s, 3H), 6.15 (d, 1H, J=15.7 Hz), 6.79 (s, 1H), 7.61 (d, 1H,J=15.7 Hz) and 7.84 (s, 1H). (Z)-isomer: 0.79 (q, 6H, J=8.0 Hz), 0.99(t, 9H, J=8.0 Hz), 3.75 (s, 3H), 5.77 (d, 1H, J=12.6 Hz), 6.74 (d, 1H,J=12.6 Hz), 7.13 (s, 1H) and 8.35 (s, 1H).

NRMS (m/e, % abundance) 266 (M⁺, 31), 238 (19), 237 (100), 209 (24), 117(37), 89 (44) and 87 (11).

Methyl 3-(2-triethylsilyl-4-furyl)propionate

A solution of (E)(Z) methyl 3-(2-triethylsilyl-4-furyl)propen-2-oate(1.83 g, 6.88 mmol) in ethyl acetate (10 ml was hydrogenated overplatinum (IV) oxide (ca 15 mg) at room temperature for 16 hours. Themixture was filtered through celite and the filtrate on evaporation gavean oil, which was purified by a silica column using 5% ethylether/hexane to give the titled ester.

¹ H NMR (CDCl₃): 0.72 (q, 6H, J=8.0 Hz), 0.79 (t, 9H, J=8.0 Hz), 2.57(t, 2H, J=7.7 Hz), 2.76 (t,2H, J=7.7 Hz), 3.68 (s, 3H), 6.50 (s, 1H) and7.44 (s, 1H).

3-(2-Triethylsilyl-4-furyl)propan-1-ol

Lithium aluminium hydride (a 1M solution in tetrahydrofuran; 5.17 ml,5.17 mmol) was added dropwise to a solution of methyl3-(2-triethylsilyl-4-furyl)propionate (1.38 g, 5.17 mmol) intetrahydrofuran (5 ml) at 0 degrees under argon. After 20 minutes, themixture was quenched with water and extracted with ethyl acetate.Evaporation of the dried (magnesium sulfate) extracts gave the desiredalcohol, which was used directly in the next step.

¹ H NMR (CDCl₃): 0.76 (q, 6H, J=8.0 Hz), 0.98 (t, 9H, J=8.0 Hz), 1.84(m, 2H), 2.52 (t, 2H, J=7.4 Hz), 3.69 (t, 2H, 6.5 Hz), 6.52 (s, 1H) and7.43 (s, 1H).

3-(2-Triethylsilyl-4-furyl)-1-propanal (Compound 5).

A mixture of dimethyl sulfoxide (0.9 ml) and dichloromethane (9 ml) wasadded to a solution of oxalyl chloride (0.64 ml, 7.39 mmol) at -78degrees under argon. After 5 minutes, a solution of3-(2-triethylsilyl-4-furyl)propan-1-ol (1.27 g, 5.28 mmol) indichloromethane (9.0 ml) was added dropwise and after 20 minutes,triethylamine (2.9 ml, 21.1 mmol) was added. Stirring was continued at-78 degrees C. for 40 minutes and at room temperature for 3 hours. Themixture was quenched with water and was extracted thoroughly with ethylether. Evaporation of the dried (magnesium sulfate) extracts gave anoil, which was purified by a silica column to give the titled aldehyde.

¹ H NMR (CDCl₃): 0.75 (q, 6H, J=7.3 Hz), 0.97 (t, 9H, J=7.3 Hz), 2.73(m, 4H), 6.49 (s, 1H), 7.43 (s, 1H) and 9.80 (s, 1H).

¹³ C NMR (CDCl₃): 2.9, 6.9, 17.1, 43.9, 121.9, 123.2, 143.5, 159.3 and202.1.

4-(4,4-Dibromo-3-butenyl)-2-triethylsilylfuran

3-(2-Triethylsilyl-4-furyl)-1-propanal (Compound 5, 500 mg, 2.09 mmol)was added to a mixture of carbon tetrabromide 868 mg, 2.62 mmol) andtriphenylphosphine (1.27 g, 5.25 mmol) in dichloromethane at 0 degreesunder argon. After 4 hours, the mixture was diluted with pentane andfiltered. Evaporation of the filtrate gave a residue, which was purifiedby a silica column using hexane to give the titled dibromide.

¹ H NMR (CDCl₃): 0.76 (q, 6H, J=8.0 Hz), 0.98 (t, 9H, J=8.0 Hz), 2.36(dt, 2H, J=7.5 Hz), 2.55 (t, 2H, J=7.6 Hz), 6.41 (t, 1H, J=7.0 Hz), 6.50(s, 1H) and 7.43 (s, 1H).

¹³ C NMR (CDCl₃) 3.2, 7.3, 14.1, 19.9, 22.7, 24.2, 25.2, 29.4, 29.5,29.6, 31.6, 31.9, 38.1, 62.7, 81.9, 84.8, 121.9, 123.3, 143.3 and 158.5.

HRMS exact mass calculated for C₂₆ H₄₆ O₂ Si (M⁺) 418.3267, found418.3258.

4-(5-Hydroxy-3-hexadecynyl)-2-triethylsilylfuran

n-Butyl lithium (a 2.5M solution in tetrahydrofuran; 0.42 ml, 1.04 mmol)was added dropwise to a solution of4-(4,4-dibromo-3-butenyl)-2-triethylsilylfuran (200 mg, 0.51 mmol) intetrahydrofuran (8 ml) at -78 degrees under argon. After 2 hours, asolution of 1-dodecanal (102 mg, 0.56 mmol) in tetrahydrofuran (1 ml)was added. Stirring was continued for 14 hours, while the cooling bathattained room temperature. The mixture was quenched with water and wasextracted with ethyl ether. Evaporation of the dried (magnesium sulfate)extracts gave a residue, which was purified by a silica column with 15%ethyl ether/hexane to give the titled alcohol.

¹ H NMR (CDCl₃): 0.76 (q, 6H, J=8.0 Hz), 0.88 (t, 3H, J=5.3 Hz), 0.95(t, 9H, J=8.0 Hz), 1.26 (m, 18H), 1.60 (m, 2H), 2.45 (t, 2H, J=7.4 Hz),2.64 (t, 2H, J=7.4 Hz), 4.34 (dd, 1H, J=6.4 Hz, 5.5 Hz), 6.55 (s, 1H)and 7.48 (s, 1H).

4-(5-Oxo-3-hexadecynyl)-2-triethylsilylfuran

Jones reagent (a 2.6M solution in sulfuric acid; 0.13 ml, 0.36 mmol) wasadded dropwise to a solution of4-(5-hydroxy-3-hexadecynyl)-2-triethylsilylfuran (136.4 mg, 0.33 mmol)in acetone (5 ml) at 0 degrees. After 20 minutes, the excess Jonesreagent was destroyed with ethanol (ca 1 ml) and the mixture wasdiluated with water. The organic phase was separated, dried (magnesiumsulfate) and evaporated down to give an oil, which was purified bypreparative silica plates to give the titled ketone.

¹ H NMR (CDCl₃): 0.76 (q, 6H, J=8.0 Hz), 0.88 (t, 3H, J=7.0 Hz), 0.98(t, 9H, J-8.0 Hz), 1.25 (m, 16H), 1.60 (m, 2H), 2.50 (t, 2H, J=7.5 Hz),2.60 (t, 2H, J=6.8 Hz), 2.71 (t, 2H, J=6.8 Hz), 6.54 (s, 1H) and 7.50(s, 1H).

¹³ C NMR (CDCl₃): 3.2, 7.3, 14.1, 20.2, 22.7, 23.3, 24.0, 28.9, 29.3,29.4, 29.6, 31.9, 45.5, 81.2, 93.1, 121.6, 122.6, 143.4, 159.0 and188.4.

HRMS exact mass calculated for C₂₆ H₄₄ O₂ Si(M⁺) 416.3105, found416.3092.

4-(5-Oxo-3-hexadecynyl)-5-hydroxy-2(5H)-furanone

A mixture of 4-(5-oxo-3-hexadecynyl)-2-triethylsilylfuran (74.4 mg, 0.18mmol), water (a few drops) and Rose Bengal (5 mg) in tetrahydrofuran (7ml) was exposed to singlet oxygen at 0 degrees for 1 hour. The residue,after solvent removal, was purified by preparative silica plates(developed with 60% ethyl ether/hexane) to give the titled furanone.

¹ H NMR (CDCl₃): 0.88 (t, 3H, J=6.9 Hz), 1.26 (m, 16H), 1.65 (m, 2H),2.53 (t, 2H, J=7.4 Hz), 2.75 (m, 4H), 4.35 (brs, 1H), 6.00 (s, 1H) and6.08 (d, 1H, J=7.4 Hz).

¹³ C NMR (CDCl₃) 13.8, 16.4, 22.4, 23.7, 25.7, 28.7, 29.1, 29.2, 29.4,31.7, 45.3, 81.6, 91.3, 99.1, 118.7, 166.8, 171.5 and 189.3.

HRMS exact mass calculated for C₂₀ H₃₁ O₄ (M+H)⁺ 335.2222, found335.2226.

3-(2-Trimethylsilyl-4-furyl)propan-1-al is treated with(triphenylphosphoranylidene) acetaldehyde in tetrahydrofuran to give5-(2-trimethylsilyl-4-furyl)-pent-2-en-1-al which is hydrogenated in thepresence of a palladium catalyst to give5-(2-trimethylsilyl-4-furyl)-pentan-1-al. Treating this intermediatewith C₉ H₁₉ COCH₂ PO)OCH₃)₂ and sodium hydride in tetrahydrofuran gives3-(7-oxo-5-hexadecenyl)-5-trimethylsilylfuran and oxidizing gives4-(7-oxo-5-hexadecenyl)-5-hydroxy-2-(5H)-furanone.

Hydrogenating 3-(7-oxo-5-hexadecenyl)-5-trimethylsilylfuran usingplatinum oxide as catalyst and oxidizing gives4-(7-oxohexadecyl)-5-hydroxy-2(5H)-furanone.

3-(2-Trimethylsilyl-4-furyl)propan-1-al is reacted with dioctylmalonatein tetrahydrofuran in the presence of acetic acid and piperidine to give3-[4,4-di(carbooctanoxy)-3-butenyl]-5-trimethylsilylfuran which istreated with cold aqueous potassium hydroxide to give3-(4-carboxy-4-carbooctanoxy-3-butenyl)-5-trimethylsilylfuran.

A mixture of the above prepared furan compound and Rose Bengal intetrahydrofuran is exposed to singlet oxygen at -78 degrees for 2 hoursto give4-(4-carboxy-4-carbooctanoxy-3-butenyl)-5-hydroxy-2(5H)-furanone.

3-(4-Carboxy-4-carbooctanoxy-3-butenyl)-5-trimethylsilylfuran is reactedwith ethanol in the presence of 1,3-dicyclohexylcarbodiimide and4-dimethylaminopyridine to give3-(4-carboethoxy-4-carbooctanoxy-3-butenyl)-5-trimethylsilylfuran.Oxidizing this intermediate gives4-(4-carboethoxy-4-carbooctanoxy-3-butenyl)-5-hydroxy-2(5H) -furanone.

EXAMPLE 6 2-Trimethylsilyl-4-vinylfuran

n-Butyl lithium (a 1.6 M solution in hexane; 2.23 ml, 3.57 mmol) wasadded dropwise to a suspension of methyltriphenylphosphonium bromide(262 mg, 0.73 mmol) in tetrahydrofuran 8 ml) at 0 degrees under argon.After 20 minutes, a solution of 5-trimethylsilyl-3-furaldehyde (102 mg,0.61 mmol) in tetrahydrofuran (1/2ml) was added. Stirring was continuedfor 18 hours while the cooling bath attained room temperature. Themixture was quenched with methanol/water (1:1, 20 ml) and extracted withpentane. Evaporation of the dried (magnesium sulphate) extracts gave anoil, which was flash chromatographed on silica using pentane. The titlevinylfuran was obtained as a colorless oil.

¹ H NMR (CDCl₃): 0.31 (s, 9H), 5.15 (d, 1H, J=10 2 Hz), 5.50 (d, 1H,J=17.6 Hz), 6.64 (dd, 1H, J=17.6 Hz, 10.2 Hz), 6.82 (s, 1H) and 7.65 (s,1H).

MS m/e (% abundance): 184 , 22), 158 (14), 108 (26), 90 (23), 74 (68)and 60 (100).

4-(1,2-Dihydroxyethyl)-2-trimethylsilyfuran

2-Trimethylsily-4-vinylfuran (272 mg, 1.64 mmol) was added to a mixtureof 4-methylmorpholine N-oxide (203 mg, 1.74 mmol), osmium tetroxide (a2.5% by weight solution in tert-butanol; 0.1 ml), water (3.5 ml) andacetone (1.5 ml) at room temperature under argon. Stirring was continuedfor 19 hours and most of the acetone was evaporated under vacuum. Sodiumbisulphite was added to the residue and the pH of the solution wasadjusted to 1 with dilute sulphuric acid. After being saturated withsodium chloride, the solution was extracted thoroughly with ethylacetate. Evaporation of the dried (magnesium sulphate) extracts affordedan oil, which was purified by preparative TLC (silica plate; developedwith 60% ethyl ether/petroleum ether). The title diol was obtained as apale yellow oil.

¹ H NMR (mixture of diasteriomers) CDCl₃): 0.29 (s, 9H), 0.35 (s, 9H),2.2 (br, 2H), 3.70-3.85 (m, 2H), 4.85 (dd, 1H, J=3.9 Hz, 7.3 Hz), 4.95(m, 2H), 6.50 (d, 1H), 6.65 (s, 1H), 7.60 (d, 1H), and 7.66 (s, 1H).

¹³ C NMR (CDCl₃) -1.8, -1.0, 66.9, 67.3, 67.7, 108.4, 118.3, 124.3,134.2, 143.7, 146.5, 156.2 and 161.5.

MS m/e (% abundance): 200 (M⁺, 18), 169 (100), 153 (22), 139 (9) and 73(73).

4-(1,2-Didodecanoyloxyethyl)-2-trimethylsilylfuran

tert-Butyl lithium (a 1.7 M solution in pentane: 0.34 ml, 0.57 mmol) wasadded dropwise to a solution of4-(1,2-dihydroxyethyl)-2-trimethylsilylfuran (52 mg, 0.26 mmol) intetrahydrofuran (1 ml) at 0 degrees under argon. After 5 minutes,lauroyl chloride (0.13 ml, 0.57 mmol) was added and stirring wascontinued at room temperature for 15 hours. The mixture was quenchedwith water and extracted with ether. Evaporation of the dried (magnesiumsulphate) extracts gave an oil, which was purified by preparative TLC(silica plate; developed with 5% ethyl ether/petroleum ether). The titlediester was obtained as a pale yellow oil.

¹ H NMR (CDCl₃): 0.28 (s, 9H), 0.91 (t, 6H, J=6.9 Hz), 1.29 (brs, 32H),1.60 (m, 4H), 2.35 (m, 4H), 4.35 (m, 2H), 6.12 (m, 1H), 6.69 (s, 1H) and7.67 (s, 1H).

4-(1.2-Didodecanoyloxyethyl)-5-hydroxy-2(5H)-furanone

A mixture of 4-(1,2-didodecanoyloxyethyl)-2-trimethylsilylfuran (97.1mg, 0.17 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (8 ml) wasexposed to singlet oxygen for 21/2 hours at -78 degrees. The residue,after solvent removal, was purified by preparative TLC (20×20 cm, 500usilica plate; developed with 60% ethyl ether/petroleum ether). The titlediester was obtained as a colorless waxy solid.

¹ H NMR (CDCl₃) 0.89 (t, 6H, J=6.9 Hz), 1.27 (brs, 16H), 1.65 (m, 4H),2.34 (t, 2H, J=7.6 Hz), 2.41 (t, 2H, J=8.0 Hz), 4.35-4.55 (m, 2H), 5.75(t, 1H), 6.09 (s, 1H) and 6.15 (s, 1H).

¹³ C NMR (CDCl₃) 14.1, 22.7, 24.8, 28.1, 28.3, 28.5, 28.6, 28.7, 29.1,29.4, 29.5, 29.6, 31.9, 34.0, 62.7, 67.6, 97.7, 121.0, 161.5, 168.9 and172.5.

MS m/e exact mass calculated for C₃₀ H₅₆ NO₇ (M+NH₄)⁺ 542.4057, found542.4054.

4-(1,2-Dihydroxyethyl)-2-triethylsilylfuran (prepared substantially asdescribed above using 5-triethylsilyl-3-furaldehyde in place of thecorresponding trimethylsilyl furaldehyde) is reacted with dodecanoylchloride in the presence of triethylamine to give4-(1-hydroxy-2-dodecanoyloxyethyl)-2-triethylsilylfuran. Treating this1-hydroxy compound with acetic anhydride and pyridine gives4-(1-acetoxy-2-dodecanoyl-oxyethyl)-2-triethylsilylfuran.

A mixture of the above prepared furan and Rose Bengal in tetrahydrofuranis exposed to singlet oxygen to give4-(1-acetoxy-2-dodecanoyloxyethyl)-5-hydroxy-2(5H) -furanone.

Reacting 4-(1,2-dihydroxyethyl)-2-triethyl-silylfuran with acetylchloride and triethylamine gives4-(1-hydroxy-2-acetoxyethyl)-2-triethylsilylfuran. Reacting thisintermediate with dodecanoyl chloride and triethylamine and oxidizingthe resulting 4-(1-dodecanoyloxy-2-acetoxyethyl)-2-triethylsilylfurangives 4-(1-dodecanoyloxy-2-acetoxyethyl)-5-hydroxy2(5H)-furanone.

Using methyl methylphosphonochloridate in place of dodecanoyl chloridein the above-described procedure for making4-(1-acetoxy-2-dodecanoyloxyethyl)-5-hydroxy-2(5H) -furanone, theproduct obtained is 4-[1-acetoxy-2-OP(O)(OCH₃)(CH₃)ethyl]-5-hydroxy-2(5H)-furanone.

4-(2-Amino-1-hydroxy)ethyl-2-triethylsilylfuran (Compound 7)

A mixture of 5-triethylsilyl-3-furaldehyde (4.35g, 20.7 mmol),trimethylsilyl cyanide (3.0 ml, 22.7 mmol) and zinc bromide (ca. 10 mg)was stirred under argon at room temperature for 19 hours. After cooledto 0°, lithium aluminum hydride (a 1.0M solution in tetrahydrofuran;31.0 ml, 31.0 mmol) was added dropwise. Stirring was continued for 3hours while the cooling bath was warmed to room temperature. The mixturewas recooled to 0° and was quenched with dilute sodium hydroxide. Afterthe aluminum salt was coagulated by the addition of sodium sulfate, themixture was filtered. Evaporation of the filtrate gave a residue whichwas purified by a silica column using 20% methanol/chloroform/0.2%triethylamine to give the title amino alcohol as a pale yellow solid.

1HNMR(CDCl₃): 0.73 (q, 6H, J=8.2 Hz), 0.97 (t, 9H, J=8.2 Hz), 2.05 (br,3H), 2.87 (dd, 1H, J=7.6 Hz, 12.7 Hz), 3.00 (dd, 1H J=12.7 Hz, 4.0Hz),4.62 (dd, 1H, J=4.0 Hz, 7.4Hz), 6.61 (s, 1H) and 7.61 (s, 1H).

4-(2-Undecanylamido-1-hydroxy)ethyl-2-triethylsilylfuran and4-(2-undecanylamido-1-dodecanoyloxy)ethyl-2-triethylsilylfuran

Dodecanoyl chloride (0.41 ml, 1.76 mmol) was added dropwise to asolution of 4-(2-amino-1-hydroxy)ethyl-2-triethylsilylfuran (Compound 7)(404.7 mg, 1.68 mmol) and triethylamine (0.25 ml, 1.76 mmol) intetrahydrofuran (4 ml) at 0°. Stirring was continued for 14 hours whilethe cooling bath attained room temperature. The mixture was evaporatedto give a residue which was purified by a silica column using 20% ethylacetate/hexane. Fractions with R_(f) of about 0.19 (20% ethylacetate/hexane) on evaporation gave4-(2-undecanylamido1-dodecanoyloxy)ethyl-2-triethylsilylfuran. Furtherelution of the column with 40% ethyl acetate/hexane gave4-(2-undecanylamido-1-hydroxy)ethyl-2-triethylsilylfuran (R_(f) 0.19;40% ethylacetate/hexane).

4-(2-Undecanylamido-1-dodecanoyloxy)ethyl-2-triethylsilylfuran: ¹HNMR(CDCl₃): 0.75 (q, 6H, J=7.9 Hz), 0.88 (t, 6H, J=6.9Hz), 0.97 (q, 9H,J=7.4 Hz),1.25 (br s 32H), 1.60 (m, 4H), 2.15 (t, 2H J=8.0 Hz), 2.33 (t,2H J=7.6 Hz), 3.68 (m, 2H), 5.65 (br t, 1H), 5.90 (br t, 1H), 6.58 (s,1H) and 7.63 (s, 1H). MS (m/e % abundance) 606[(M+H)⁺, 1], 450(2),424(4), 423(10), 408(10), 407(32), 406(100), 405(5), 224(8), 200(2),183(2) and 104(2).

4-(2-Undecanylamido-1-hydroxy)ethyl-2-triethylsilylfuran: ¹ HNMR(CDCl₃): 0.75 (q, 6H, J=7.9 Hz), 0.89 (t, 3H, J=7.1 Hz), 0.98 (q, 9H,J=7.1 Hz), 1.27 (br s, 16H), 1.65 (m, 2H), 2.21 (t, 2H, J=7.3 Hz), 3.08(d, 1H, J=3.8 Hz), 3.38 (2dd, 1H, J=15.0 Hz, 7.5 Hz and 6.0 Hz), 3.70(2dd, 1H, J=15.0 Hz, 7.5 Hz and 3.0 Hz), 4.85 (m, 1H), 5.95 (br t, 1H),6.62 (s, 1H). HRMS exact mass calculated for C₂₄ H₄₅ SiNO₃ (M⁺)423.3169, found 423.3166.

4-(2-Undecanylamido-1-hydroxy)ethyl-5-hydroxy-2(5H1-furanone (Compound40)

A mixture of 4-(2-undecanylamido-1-hydroxy)ethyl-2-triethylsilylfuran(300 mg, 0.71 mmol), water (a few drops) and Rose Bengal (5 mg) inacetone (7 ml) was exposed to singlet oxygen at 0° for 1 hour. Theresidue, after solvent removal, was purified on preparative silicaplates (developed with 5% methanol/dichloromethane) to give the titlefuranone.

¹ HNMR(CD₃ OD): 0.90 (br t, 3H), 1.29 (br s, 16H), 1.55 (m, 2H), 2.19(t, 2H, J=7.3 Hz), 3.50 (br m, 2H), 4.60 (br, 1H), 6.06 (s, 1H) and 6.15(br s, 1H).

¹³ CNMR(CD₃ OD): 14.5, 23.7, 23.9, 27.0, 27.1, 29.8, 29.9, 30.0, 30.2,30.4, 30.6, 30.7, 31.1, 31.3, 33.0, 33.2, 36.9, 44.4, 44.5, 44.6, 68.2,100.3, 100.4, 119.6, 171.2, 172.6 and 176.9. HRMS exact mass calculatedfor C₁₈ H₃₁ NO₅ (M⁺) 342.2280 found 342.2293.

4-(1-Acetoxy-2-undecanylamido)ethyl-2-triethylsilylfuran

A mixture of 4-(2-undecanylamido-1-hydroxy)ethyl-2-triethylsilylfuran(244.3 mg, 0.58 mmol), acetic anhydride (0.5 ml) and pyridine (0.5 ml)was stirred at room temperature for 16 hours. After most of the solventwas removed, the residue was purified by preparative silica TLC using60% ethyl ether/hexane to give the title ester as a colorless solid.

¹ HNMR(CDCl₃): 0.77 (q, 6H, J=7.5 Hz), 0.91 (t, 3H, J=6.8 Hz), 1.00 (t,9H, J=7.3 Hz), 1.29 (br s, 16H), 1.60 (m, 2H), 2.13 (s, 3H), 2.19 (t,2H, J=7.9 Hz), 3.70 (m, 2H), 5.70 (br t, 1H), 6.95 (m, 1H), 6.63 (s, 1H)and 7.67 (s, 1H). HRMS exact mass calculated for C₂₆ H₄₇ NO₄ Si(M⁺)465.3274, found 465.3283.

4-(1-Acetoxy-2-undecanylamido)ethyl-5-hydroxy-2(5H)-furanone (Compound41)

A mixture of 4-(1-acetoxy-2-undecanylamido)ethyl-2-triethylsilylfuran(160 mg, 0.34 mmol), water (a few drops) and Rose Bengal (3 mg) inacetone (7 ml) was exposed to singlet oxygen at 0° for 2 hours. Theresidue, after solvent removal, was purified by preparative silicaplates (developed with 40% ethyl acetate/hexane) to give the titlefuranone.

¹ HNMR(CDCl₃): 0.89 (t, 3H, J=6.8 Hz), 1.27 (br s, 16H), 1.65 (m, 2H),2.18 (s, 3H), 2.20 (m, 2H), 3.35 (br m, 1H), 4.25 (br m, 1H), 5.60 (brs,1H), 5.95 (br s, 1H), 6.10 (m, 1H), 6.20 (m, 1H) and 7.20 (br m, 1H).

¹³ CNMR(CDCl₃): 14.0, 20.7, 22.6, 25.6, 25.7, 28.8, 28.9, 29.1, 29.2,29.4, 29.5, 29.8, 31.8 36.2, 40.9, 41.0, 41.1, 50.5, 69.3, 69.4, 69.5,98.7, 120.2, 120.3, 120.4, 169.5, 169.7, 175.9, 176.0 and 176.1

HRMS exact mass calculated from C₂₀ H₃₄ NO₆ (M⁺) 384.2386, found384.2381.

4-(2-Undecanylamido-1-dodecanoyloxy)ethyl-5-hydroxy-2(5H)-furanone(Compound 42)

A mixture of 4-(2-undecanylamido-1-dodecanoyl)ethyl-2-triethylsilylfuran(145 mg, 0.24 mmol), Rose Bengal (ca. 5 mg) and a few drops of water intetrahydrofuran (7 ml) was exposed to singlet oxygen at 0° for 1 hour.The residue, after solvent removal, was purified by preparative silicaTLC plates using 40% ethyl acetate/hexane to give the title furanone asa pale yellow oil. ¹ HNMR(CDCl₃): 0.93 (t, 6H, J=7.0 Hz), 1.31 (br s,32H), 1.60 (m, 4H), 2.25 (m, 2H), 2.40 (t, 2H, J=7.6 Hz), 3.35 (2 br t,1H), 4.30 (m, 1H), 5.64 (br s, 1H), 5.96 (s, 1H), 6.05-6.20 (m, 3H) and7.65 (br m 1H). MS (m/e, % abundance): 523(M⁺, 15), 522 ( 13), 521 (24),339 (12), 326 (12), 324 (16), 310 (25), 309 (21), 308 (100), 307 (19),306 (28), 264 (18), 218 (23), 201 (71), 200 (64), 183 (60), 181 (43),126 (81), 125 (67), 98 (43) and 83 (39).

4[-(1-Hydroxy-2-dodecanesulfonylamido)ethyl]-2-triethylsilylfuran

A mixture of 4-(2-amino-1-hydroxy)ethyl-2-triethylsilylfuran (Compound7, 694.2 mg, 2.88 mmol), dodecanesulfonyl chloride (930 mg, 3.45 mmol)and triethylamine (0.48 ml, 3.45 mmol) in tetrahydrofuran (10 ml) wasstirred at room temperature for 2 days. The mixture was quenched withwater and was extracted with ethyl ether. Evaporation of the dried(magnesium sulfate) extracts gave an oil, which was purified by a silicacolumn using 55% ethyl ether/hexane to give the title compound. ¹HNMR(CDCl₃): 0.76 (q, 6H, J=8.0 Hz), 0.88 (t, 3H, J=6.9 Hz), 0.98 (t,9H, J=8.0 Hz), 1.26 (m, 16H), 1.38 (m, 2H), 1.81 (m, 2H), 2.21 (m, 1H),3.0 (m, 2H), 3.35 (m, 2H), 4.62 (m, 1H), 4.85 (m 1H), 6.61 (s, 1H) and7.65 (s, 1H). ¹³ CNMR(CDCl₃): 3.0, 7.1, 13.9, 22.5, 23.4, 28.2, 29.0,29.1, 29.2, 29.4, 29.5, 31.8 49.3, 52.6, 66.4, 119.0, 125.3, 143.7 and159.4. HRMS exact mass calculated for C₂₄ H₄₇ NO₄ SSi:(M⁺) 473.2995found 473.3004.

4-(1-Hydroxy-2-dodecanesulfonylamido)ethyl]-5-hydroxy-2(5H)-furanone

A mixture of4-[(1-hydroxy-2-dodecanesulfonylamido)ethyl]-2-triethylsilylfuran (200mg, 0.42 mmol), water (a few drops) and Rose Bengal (5 mg) in acetone(10 ml) was exposed to singlet oxygen at 0° for 2 hours. The residue,after solvent removal, was purified by preparative silica plates(developed with 20% methanol/dichloromethane) to give the titledfuranone. ¹ HNMR(CDCl₃): 0.88 (t, 3H, J=6.9 Hz), 1.26 (m, 18H), 1.75 (m,2H), 3.05 (m, 2H), 3.30 (m, 1H), 3.42 (m, 1H), 4.69 (br, 1H), 6.20 (br,1H) and 6.29 (br, 1H). ¹³ CNMR(CDCl₃): 13.9, 22.5 23.3, 28.2, 29.1,29.2, 29.3, 29.5, 31.7, 46.3, 46.4, 52.6, 67.3, 67.4, 98.3, 98.4, 119.9,167.0, 168.0, 172.2 and 172.3. HRMS exact mass calculated for C₁₈ H₃₅ N₂O₅ S[(M+NH₄)-H₂ O]391.2267, found 391.2249.

4-[1-Acetoxy-2-(dodecansulfonylamido)ethyl]-2-triethylsilylfuran

A mixture of4-[1-hydroxy-2-(dodecansulfonylamido)ethyl]-2-triethylsilylfuran (228mg, 0.48 mmol), acetic anhydride (55 ul, 0.58 mmol) and pyridine (47 ul,0.58 mmol) in dichloromethane (5 ml) was stirred at room temperature for14 hours. After most of the solvent was removed, the residue wasredissolved in ether and washed with aqueous copper sulfate and water.Evaporation of the dried (magnesium sulfate) organic phase gave an oil,which was purified by a silica column using 45% ethyl ether/hexane togive the titled ester. ¹ HNMR(CDCl₃): 0.76 (q, 6H, J=7.4 Hz), 0.88 (t,3H, J=5.9 Hz), 0.97 (t, 9H, J=7.4 Hz), 1.25 (m, 18H), 1.76 (m, 2H), 2.10(s, 3H), 2.97 (m, 2H), 3.50 (t, 2H, J=5.9 Hz), 4.30 (m, 1H), 5.87 (t,1H, J=5.9 Hz), 6.59 (s, 1H) and 7.66 (s, 1H).

4-[1-Acetoxy-2-(dodecanesulfonylamido)ethyl]-5-hydroxy-2(5H)-furanone(Compound 43)

A mixture of4-[1-acetoxy-2-dodecanesulfonylamido)ethyl]-2-triethylsilylfuran (196mg, 0.38 mmol), water (2 drops) and Rose Bengal (5 mg) in acetone (15ml) was exposed to singlet oxygen at 0° for 2 hours. The residue, aftersolvent removal, was purified by preparative silica plates (developedwith 10% methanol/chloroform) to give the title furanone. ¹ HNMR(CDCl₃)0.88 (t, 3H, J=6.4 Hz), 1.25 (m, 18H), 1.75 (m, 2H), 2.17 (s, 3H), 3.0(m, 2H), 3.57 (br s, 2H), 5.60 (m, 1H), 6.16 (s, 1H) and 6.18 (s, 1H).¹³ CNMR(CDCl₃): 14.1, 18.2, 20.7, 22.6, 23.5, 28.2, 29.0, 29.1, 29.3,29.5, 29.6, 29.8, 44.4, 53.4, 58.4, 69.1, 98.1 121.2, 162.7, 169.9 and170.1 LRMS (m/e, % abundance) 391 (M⁺, 28), 390(15), 389(37), 376(23),375(100), 374(12), 358(38), 356(18), 328(23), 327(12), 312(14), 268(14),267(84), 252(49), 208(28), 207(11 ) , 201(15) and 185(15).

4-(1-Hydroxy-2-(10-carboxydecaneamido)1ethyl-2-triethylsilylfuran

A mixture of 4-(2-amino-1-hydroxy)ethyl-2-triethylsilyl-furan (Compound7, 208.0 mg, 0.86 mmol), dodecanedioic acid (199.0 mg, 0.86 mmol),dicyclohexylcarbodiimide (178 mg, 0.86 mmol) and 4-dimethylaminopyridine(105 mg, 0.86 mmol) in dichloromethane (5 ml) was stirred at roomtemperature for 16 hours. The mixture was quenched with dilutehydrochloric acid and was extracted with ethyl acetate. Evaporation ofthe dried (magnesium sulfate) extracts gave a residue, which waspurified by a silica column using 5% methanol/chloroform to give thetitle furan. ¹ HNMR(CDCL3): 0.76 (q, 6H, J=8.0 Hz), 0.97 (t, 9H, J=8.0Hz), 1.29 (br s, 12H), 2.21 (t, 2H, J=7.9 Hz), 2.35 (t, 2H, J=7.2 Hz),3.35 (m, 1H), 3.60 (m, 1H), 4.83 (dd, 1H, J=7.8 Hz, 3.0 Hz), 6.10 (t,1H, J=2.9 Hz), 6.61 (s, 1H) and 7.62 (s, 1H). ¹³ CNMR(CDCl₃): 3.1, 7.2,24.6, 24.7, 24.8, 25.6, 28.8, 28.9, 29.0, 29.1, 33.6, 34.0, 36.5, 46.2,66.5, 119.1, 126.0, 143.5, 159.6, 174.8 and 178 4. HRMS exact masscalculated for C₂₄ H₄₃ SiNO₅ (M⁺) 453.2911, found 453.2913.

4-[(1-Hydroxy-2-(10-carboxydcecaneamido)]ethyl-5-hydroxy-2(5H)-furanone

A mixture of4-[(1-hydroxy-2-(10-carboxydecaneamido)]ethyl-2-triethylsilylfuran (15mg, 0.19 mmol), water (a few drops) and Rose Bengal (5 mg) in acetone (7ml) was exposed to singlet oxygen at 0° for 2 hours. The residue, aftersolvent removal, was purified by a silica column using 10%methanol/chloroform to give the title furanone. ¹ H NMR (CDCl₃): 1.29(m, 12H), 1.60 (m, 4H), 2.18 (t, 2H, J=7.0 Hz), 2.27 (t, 2H, J=7.4 Hz),3.40 (m 1H), 3.55 (m, 2H), 6.03 (br, 1H), and 6.19 (br, 1H). ¹³CNMR(CDCl₃): 26.0, 27.0, 30.1, 30.2, 30.3, 30.4, 30.5, 34.9, 36.9, 44.4,49.7, 68.4, 99.7, 119.4, 172.0, 172.6, 176.9 and 177.7. LRMS (m/e, %abundance) 371 (M⁺, 32), 355(17), 358 (38), 249(14), 248(100), 230(41)and 229(11).

4-(1-Acetoxy-2-(10-carboxydecaneamido]ethyl-2-triethylsilylfuran

A mixture of4-[(1-hydroxy-2-(10-carboxydecaneamido)]ethyl-2-triethylsilylfuran (53.4mg, 0.12 mmol), triethylamine (60 ul, 0.45 mmol) and acetic anhydride(42 ul, 0.45 mmol) in dichloromethane (5 ml) was stirred at roomtemperature for 14 hours. The mixture was quenched with dilutehydrochloric acid and was extracted with ethyl acetate. Evaporation ofthe dried (magnesium sulfate) extracts gave an oil, which was purifiedby a silica column using 5% methanol/chloroform to give the titlefuranone. ¹ HNMR(CDCl₃): 0.76 (q, 6H, J=8.0 Hz), 0.97 (t, 9H, J=8.0 Hz),1.27 (m, 6H), 1.63 (m, 4H), 2.09 (s, 3H), 2.16 (t, 2H, J=8.0 Hz), 2.34(t, 2H, J=7.4 Hz), 3.67 (m, 2H), 5.76 (br t, 1H), 5.90 (dd, 1H, J=7.2Hz, 5.0 Hz), 6.59 (s, 1H) and 7.64 (s, 1H). ¹³ CNMR(CDCl₃): 2.9, 7.0,20.9, 24.5, 24.7, 25.3, 25.4, 28.6, 28.7, 28.9, 33.4, 33.8, 36.5, 43.1,67.7, 119.5, 122.1, 144.9, 160.3, 171.0, 173.8 and 178.9. HRMS exactmass calculated for C₂₆ H₄₅ NO₆ Si(M⁺) 495.3016, found 495.2997.

4[-(1-Acetoxy-2-(10-carboxydecaneamido)]ethyl-5-hydroxy-2(5H)-furanone(Compound 44)

A mixture of4-[(1-acetoxy-2-(10-carboxydecaneamido)]ethyl-2-triethylsilylfuran (53.6mg, 0.12 mmol), water (a few drops) and Rose Bengal (3 mg) in acetone (7ml) was exposed to singlet oxygen at 0° for 2 hours. The residue, aftersolvent removal, was purified by preparative silica plates (developedwith 10% methanol/chloroform) to give the title furanone. ¹ HNMR(CDCl₃):1.26 (m, 12H), 2.55 (m, 4H), 2.15 (m, 5H), 2.35 (t, 2H, J=7.3 Hz), 3.35(m, 1H), 3.45 (br, 1H), 3.90 (br, 1H), 4.20 (m, 1H), 5.59 (br, 1H), 5.65(br, 1H), 5.97 (br, 1H), 6.00 (br, 1H) 6.10 (br, 1H), 6.15 (br, 1H),6.30 (br, 1H) and 6.40 (br, 1H). ¹³ CNMR(CDCl₃) 20.8, 24.6, 25.5, 28.8,29.0, 29.1, 29.3, 33.8, 36.3, 41.4, 69.8, 98.6, 120.4, 163.1, 169.1,169.2, 176.0 and 178.8. LRMS (m/e % abundance) 395[(M⁺ -H₂ O), 0.4],369(7), 355(10), 354(14), 353(40), 336(12), 249(14), 248(100) and230(29).

N-(Methanesulfonyl)piperazine

A mixture of methanesulfonyl chloride (1.85 ml, 24 mmol) and piperazine(2.06 g, 24 mmol) in dichloromethane (60 ml) was stirred at roomtemperature for 14 hours. The mixture was basified with aqueous sodiumhydroxide and filtered The filtrate was washed with water, dried(magnesium sulfate) and evaporated down to give the title sulfonamide. ¹HNMR(CDCl₃): 1.75 (br s, 1H), 2.78 (s, 3H), 2.97 (t, 4H, J=5.1 Hz) and3.19 (t, 4H, J=7.5 Hz). LRMS (m/e, % abundance) 165[(M+H)⁺, 7), 164(M⁺,5), 85(100) and 56(68).

4-[1-Hydroxy-2-(N'-methanesulfonylpiperazine)amido]ethyl-2-triethylsilylfuranand 4-[1-hydroxy-2-(N',N'-diethyl)amido]ethyl-2-triethylsilylfuran

Phosgene (a 20% solution in toluene; 0.46 ml, 0.90 mmol) was addeddropwise to a mixture of N-(methanesulfonyl)piperazine (147.4 mg, 0.90mmol) and triethylamine (0.13 ml, 0.90 mmol) in dichloromethane (3 ml)at room temperature. After 1 hour,4-(2-amino-1-hydroxy)ethyl-2-triethylsilylfuran (Compound 7, 217 mg,0.90 mmol) was added. Stirring was continued at room temperature for 14hours. The mixture was quenched with water and was extracted with ethylacetate. Evaporation of the dried (magnesium sulfate) extracts gave aresidue, which was purified by a silica column using 80% ethylacetate/hexane to give4-[1-hydroxy-2-(N',N'-diethyl)amido]-ethyl-2-triethylsilylfuran (R_(f)0.27, 80% ethylacetate/hexane). Subsequent elution with ethyl acetategave4-[1-hydroxy-2-(N'-methanesulfonylpiperazine)amido]-ethyl-2-triethylsilylfuran(R_(f) 0.21; ethyl acetate/hexane).

4-[1-Hydroxy-2-(N'-methanesulfonylpiperazine)amido]ethyl-2-triethylsilylfuran,¹ HNMR(CDCl₃): 0.79 (q, 6H, J=8.0 Hz), 1.00 (t, 9H, J=8.I Hz), 1.70 (br,1H), 2.83 (s, 3H), 3.26 (t, 4H, J=4.8 Hz), 3.40 (m, 1H), 3.55 (t, 4H,J=4.8 Hz), 3.60 (m, 1H), 4.84 (dd, 1H, J=7.9 Hz, 3.2 Hz), 5.03 (br, 1H),6.64 (s, 1H) and 7.65 (s, 1H). HRMS exact mass calculated for C₁₈ H₃₃ N₂O₅ SSi(M⁺) 431.1895.4-[1-Hydroxy-2-(N',N'-diethyl)amido]ethyl-2-triethylsilylfuran ¹HNMR(CDCl₃): 0.73 (q, 6H, J=7.5 Hz), 1.00 (t, 9H, J=7.4 Hz), 1.16 (t,6H, J=7.1 Hz), 3.30 (q, 4H, J=7.1 Hz), 3.40 (m, 1H), 3.65 (m, 1H), 4.33(d, 1H, J=4.1 Hz), 4.80 (br t +m, 2H), 6.65 (s, 1H) and 7.64 (s, 1H).HRMS exact mass calculated for C₁₇ H₃₂ N₂ O₃ Si(M⁺) 340.2171.

4-[1-Dodecanoyloxy-2-(N'-methanesulfonylpiperazine)amido1ethyl-2-triethylsilyfuran

A mixture of4-[1-hydroxy-2-(N'-methanesulfonylpiperazine)amido]-ethyl-2-triethylsilylfuran100 mg, 0.23 mmol), dodecanoyl chloride (95 ul, 0.41 mmol) andtriethylamine (40 ul, 0.28 mmol) in dichloromethane (7 ml) was stirredat room temperature for 14 hours. The mixture was quenched with waterand was extracted with ethyl acetate.

Evaporation of the dried (magnesium sulfate) extracts gave an oil, whichwas purified by preparative silica plates (developed with 45%ethylacetate/hexane) to give the title furan. ¹ HNMR(CDCl₃): 0.76 (q,6H, J=8.0 Hz), 0.88 (t, 3H, J=6.0 Mz), 0.97 (t, 9H, J=8.0 Hz), 1.25 (m,14H), 2.34 (t, 2H, J=7.6 Hz), 2.79 (s, 3H), 3.21 (t, 4H, J=4.9 Hz), 3.46(m, 4H), 3.65 (m, 2H), 4.92 (br t, 1H), 5.94 (dd, 1H, J=8.0 Hz, 4.0 Hz),6.59 (s, 1H) and 7.64 (s, 1H). ¹³ CNMR(CDCl₃): 3.1, 7.2, 14.0, 22.6,24.9, 29.0, 29.2, 29.4, 29.5, 31.8, 34.5, 43.6, 45.4, 45.5, 68.1, 119.3,122.1, 144.4, 156.8, 159.9 and 173.9. HRMS exact mass calculated forC.sub. 30 H₅₅ N₃ O₆ SSi(M⁺) 413.3581, found 413.3562.

4-[1-Dodecanoyloxy-2-(N'-methanesulfonylpiperazine)amido]ethyl-5-hy(Compound 45)

A mixture of4-[I-dodecanoyloxy-2-(N'methanesulfonylpiperazine)amido]ethyl-2-triethylsilylfuran(61 mg, 0.11 mmol), water (a few drops) and Rose Bengal (3 mg) inacetone (7 ml) was exposed to singlet oxygen at 0° for 2 hours. Theresidue, after solvent removal, was purified by a silica column using7.5% methanol/chloroform to give the title furanone. ¹ HNMR(CDCl₃): 0.88(t, 3H, J=6.9 Hz), 1.26 (m, 16H), 1.61 (m, 2H), 2.40 (t, 2H, J=6.9 Hz),2.80 (s, 3H), 3.19 (t, 4H, J=5.0 Hz), 3.50 (m, 5H), 4.18(m, 1H), 5.05(m, 1H), 5.56 (br d, 1H, J=1.3 Hz), 5.90 (br, 1H), 6.12 (br, 1H) and7.65 (m, 1H). ¹³ CNMR(CDCl₃) 14.5, 23.0, 25.1, 29.5, 29.6, 29.7 29.8,30.0, 32.2, 34.4, 35.1, 43.1, 44.1, 45.7, 70.1, 99.3, 120.6, 158.0,169.8, 169.9 and 172.6. HRMS exact mass calculated for C₂₄ H₄₀ N₃ O₇ S(M⁺ -OH) 514.2587, found 514.2591.

4[-1-Dodecanoyloxy-2-(N',N'-diethyl)amido]ethyl-2-triethylsilylfuran

A mixture of4-[1-hydroxy-2-(N',N'-diethyl)amido]ethyl-2-triethylsilylfuran (80 mg,0.24 mmol), dodecanoyl chloride 65 ul, 0.28 mmol) and triethylamine (40ul, 0.28 mmol) in dichloromethane (7 ml) was stirred at room temperaturefor 14 hours. The mixture was quenched with water and was extractedthoroughly with ethyl acetate. Evaporation of the dried (magnesiumsulfate) extracts gave an oil, which was purified by preparative silicaplates (developed with 60% ethyl ether/hexane) to give the title furan.¹ HNMR(CDCl₃): 0.75 (q, 6H, J=8.0 Hz), 0.88 (t, 3H, J=7.0 Hz), 0.96 (t,9H, J=8.0 Hz), 1.10 (t, 6H, J=7.2 Hz), 1.25 (m, 14H), 1.58 (m, 4H), 2.33(t, 2H, J=7.7 Hz), 3.22 (q, 4H, J=7.2 Hz), 3.64 (m, 2 H), 4.61 (br t,1H), 5.93 (dd, 1H, J=7.4 Hz, 4.8 Hz), 6.61 (s, 1H) and 7.64 (s, 1H). ¹³CNMR(CDCl₃): 2.8, 6.9, 13.5, 13.8, 22.4, 24.8, 28.9, 29.0, 29.1, 29.2,29.4, 31.7, 34.3, 41.1, 44.8, 68.1, 119.6, 122.6, 144.8, 157.2, 159.9and 173.9. HRMS exact mass calculated for C₂₉ H₅₄ N₂ O₄ Si (M⁺)522.3853, found 522.3859.

4-[1-Dodecanoyloxy-2-(N',N'-diethyl)carboxyamido]ethyl-5-hydroxy-2(5H)-furanone(Compound 46)

A mixture of4-[1-dodecanoyloxy-2-(N',N'-diethyl)amido]ethyl-2-triethylsilylfuran(39.5 mg, 0.07 mmol), water (a few drops) and Rose Bengal (5 mg) inacetone (6 ml) was exposed to singlet oxygen at 0° for 2 hours. Theresidue, after solvent removal, was purified by a silica column using10% methanol/chloroform to give the title furanone. ¹ HNMR(CDCl₃): 0.79(t, 3H, J=6.2 Hz), 1.18 (m, 16H), 1.56 2H, J=7.3 Hz), 1.74 (p, 2H, J=7.5Hz), 2.13 (t, 2H, J =7.5 Hz), 2.19 (t, 2H, J=7.5 Hz), 2.55 (t, 1H), 3.50(br m, 2H), 5.64 (br, 1H), 5.99 (br, 1H) and 6.11 (br, 1H). ¹³CNMR(CDCl₃) 14.4, 22.3, 23.7, 25.8, 30.2, 30.4, 30.5, 30.6, 30.8, 33.1,34.1, 34.8, 35.9, 41.9, 70.0, 100.0, 120.4, 166.3, 171.9, 174.0 and176.0.

EXAMPLE 8 2-Triethylsilyl-4-Vinylfuran

n-Butyl lithium (a 2.5 M solution in hexane; 4.4 ml, 11.0 mmol) wasadded dropwise to a suspension of methyltriphenylphosphonium bromide(3.93 g, 11 mmol) in THF (40ml) at 0 degrees C. under argon. After 2hours stirring at 0 degrees C., a solution of2-triethylsilyl-4-furaldehyde (1.54 g, 7.33 mmol) in THF (2 ml) wasadded. Stirring was continued at room temperature for 14 hours and themixture was quenched with methanol/water 40 ml (1:1). Extraction(pentane) and evaporation of the dried (magnesium sulfate) extracts gavea residue, which was purified by flash chromatography on silica usingpentane to give the titled furan. R_(f) (pentane) 0.75.

¹ H NMR (CDCl₃) 0.81 (q, 6H, J=8.1 Hz), 0.99 (t, 9H J=7.4 Hz), 5.14 (d,1H, J=12.1 Hz), 5.48 (d, 1H, J=17.6 Hz), 6.64 (dd, 1H, J=10.8 Hz, 17.5Hz), 6.81 (s, 1 H) and 7.64 (s, 1H). HRMS exact mass calculated for C₁₂H₂₀ SiO(M⁺) 208.1283, found 208.1280.

4-(1,2-Dihydroxyethyl)-2-triethylsilylfuran (Compound 6)

2-Triethylsilyl-4-vinylfuran (1.20g, 6.25 mmol) was added to a mixtureof 4-methylmorpholine N-oxide (788.0 mg, 6.70 mmol) osmium tetroxide (a2.5% by weight solution in tert-butanol; 0.50 ml), water (1.5 ml) andacetone (1.5 ml) at room temperature. After stirring for 14 hours, themixture Was acidified to pH=1 with dilute sulfuric acid. Extraction(ethyl acetate) and evaporation of the dried (magnesium sulfate)extracts gave an oil, which was purified by flash chromatography onsilica using 40% ethyl acetate/hexane to give the titled diol. R_(f)(40% ethyl acetate/hexane) 0.11.

¹ H NMR (CDCl₃) 0.80 (q, 6H, J=7.5 Hz), 0.98 (t, 9H, J=7.5 Hz), 1.65(br, 2H), 3.75 (m, 2H), 4.82 (dd, 1H, J=7.4 Hz, 3.9 Hz), 6.66 (s, 1H)and 7.68 (s, 1H). HRMS exact mass calculated for C₁₂ H₂₂ O₃ Si(M⁺)242.1338, found 242.1344.

4-(1,2-Diazidoethyl)-2-triethylsilylfuran

A solution of diphenylphosphoryl azide (0.87 ml, 4.04 mmol) in THF (1ml) was added over a period of 15 minutes to a solution of4-(1,2-dihydroxyethyl)-2-triethylsilylfuran (490 mg, 2.02 mmol),triphenylphosphine (1.06 g, 4.04 mmol) and diethylazidodicarboxylate(703 mg, 4.04 mmol) in THF (10 ml). Stirring was continued at roomtemperature for 2 days. The mixture was evaporated in the presence of aminimum amount of silica gel and the residue was purified by flashchromatography on silica using 10% ethyl ether/hexane to give the titledazide. R_(f) (10% ethyl ether/hexane) 0.48.

¹ H NMR (CDCl₃) 0.78 (q, 6H, J=8.0 Hz), 0.98 (t, 9H, J=8.0 Hz), 3.49 (d,2H, J=6.0 Hz), 4.62 (t, 1H, J=6.0 Hz), 6.62 (s, 1H) and 7.70 (s, 1H).

4-(1,2-Diaminoethyl)-2-triethylsilylfuran (Compound 8)

A solution of lithium aluminum hydride (a 1.0 M solution in THF; 1.16ml, 1.16 mmol) was added dropwise to a solution of4-(1,2-diazidoethyl)-2-triethylsilylfuran (153.6 mg, 0.53 mmol) in THF(5 ml) at 0 degrees C. under argon. After stirring at room temperaturefor 2 hours, the mixture was recooled to 0 degrees C. and quenchedslowly with 2M sodium hydroxide. The mixture was filtered and thefiltrate was extracted thoroughly with ethyl acetate. Evaporation of thedried (magnesium sulfate) extracts gave an oil, which was purified by asilica column using 10% methanol/chloroform/ammonia to give the titleddiamine.

¹ H NMR (CDCl₃) 0.76 (q, 6H, J=8.0 Hz), 0.98 (t, 9H, J=7.3 Hz), 1.00(br, 4H), 2.78 (dd, 1H, J=l2.6 Hz, 6.8 Hz), 2.89 (dd, 1H, J=12.6 Hz, 5.1Hz), 3.86 (t, 1H, J=6.4 Hz), 6.60 (s, 1H) and 7.56 (s, 1H).

An alternative synthetic route for the preparation of Compound 8 startswith 2-triethylsilyl-4-furaldehyde, to which sodium cyanide andammonia/ammonium chloride are added, followed by reduction of theresulting intermediate 2-triethylsilyl-4-(amino-cyanomethyl)furan withlithium aluminum hydride, to yield the title compound.

EXAMPLE 9 Bis-[(2-triethylsilyl-4-furyl)methyl]oxalate

Oxalyl chloride (0.59 ml, 6.79 mmol) was added dropwise to a solution of4-hydroxymethyl-2-triethylsilylfuran (Compound 1, 1.2 g, 5.66 mmol) andtriethylamine (0.95 ml, 6.79 mmol) in dichloromethane (10 ml) at 0°.After 10 minutes, the reaction mixture was quenched with ice. Extraction(dichloromethane) and evaporation of the dried (magnesium sulfate)extracts gave an oil, which was purified by flash chromatography onsilica using 5% ethyl ether/hexane. Fractions with R_(f) of about 0.17gave, after evaporation the title oxalate ester as a colorless oil.

¹ HNMR (CDCl₃) 0.81 (q, 6H, J=7.3 Hz), 1.02 (t, 9H, J-7.3 Hz), 5.24 (s,2H), 6.73 (s, 1H) and 7.78 (s, 1H).

MS m/e (% abundance) 195(100), 1 67(16), 115(35) and 87(29).

4-Iodomethyl-2-triethylsilylfuran (Compound 9)

A mixture of bis-[(2-triethylsilyl-4-furyl)methyl]oxalate (823 mg, 1.72mmol) and sodium iodide (5.36 g, 35.8 mmol) in acetone (7 ml) wasstirred at room temperature for 1 day and quenched with water.Extraction (pentane) and evaporation of the dried (magnesium sulfate)extracts gave the titled iodide, which was used in the next step withoutfurther purification.

4-Dodecanthiolmethyl-2-triethylsilylfuran

Dodecanthiol (0.52 ml, 2.19 mmol) was added dropwise to a suspension ofpotassium hydride (88 mg, 2.19 mmol) in tetrahydrofuran (10 ml) at roomtemperature under argon. After 3 hours, hexamethylphosphoramide (2 ml),followed by a solution of 4-iodomethyl-2-triethylsilylfuran (Compound 9,470 mg, 1.45 mmol) in tetrahydrofuran (2 ml) was added. Stirring wascontinued for 8 days at room temperature and the reaction mixture wasquenched with water. Extraction (ethyl ether) and evaporation of thedried (magnesium sulfate) extracts gave a residue, which was purified byflash chromatography on silica using 5% ethyl ether/hexane. Fractionswith R_(f) of about 0.18 gave after evaporation the title thioether as acolorless oil.

¹ HNMR (CDCl₃) 0.76 (q, 6H, J=7.7 Hz), 0.79 (t, 3H, J=6.7 HZ), 0.98 (t,9H, J=7.3 Hz), 1.28 (br s, 18H), 1.55 (m, 2H) 2.47 (t 2H J=7.6 Hz), 3.58(s, 2H), 6.66 (s, 1H) and 7.56 (s, 1H).

HRMS exact mass calculated for C₂₃ H₄₄ SSiO(M⁺) 396.2882, found396.2885.

4-Dodecanethiomethyl-5-hydroxy-2(5H)-furanone (Compound 47)

A mixture of 4-dodecanthiomethyl-2-triethylsilylfuran (180 mg, 0.46mmol), water (0.01 ml) and Rose Bengal (ca. 3 mg) in tetrahydrofuran (6ml) was exposed to singlet oxygen at 0° for 1 hour. The residue, aftersolvent removal, was purified by chromatography on preparative silicathin layer plates (developed with 60% ethyl ether/hexane) to give thetitle furanone as a pale yellow oil.

¹ HNMR (CDCl₃) 0.91 (t, 3H, J=6.9 Hz), 1.29 (br s, 18H), 1.6l (m, 2H),2.52 (t, 2H, J=7.2 Hz), 3.50 (br, 2H), 5.85 (br, 1H), 6.00 (s, 1H) and6.28 (s, 1H).

¹³ CNMR (CDCl₃) 14.1, 22.6, 27.6, 28.7, 28.9, 29.2, 29.3, 29.5, 29.6,31.9, 32.1, 98.3, 118.8, 165.7 and 171.5.

HRMS exact mass Calculated for C₁₇ H₃₀ SO₃ (M⁺) 314.1915, found314.1911.

4-(Dodecanesulfoxomethyl)-5-hydroxy-2(5H)-furanone

A mixture of 4-dodecanethiomethyl-5-hydroxy-2-(5H)-furanone (Compound47, 36.1 mg, 0.12 mmol) and 30% hydrogen peroxide (1 ml) in methanol(1.5 ml) was stirred at room temperature for 18 hours. Most of thesolvent was removed and the residue was purified by chromatography onpreparative silica thin layer plates (developed with ethyl acetate) togive the title furanone.

¹ HNMR (CDCl₃) 0.89 (t, 3H), 1.25 (br s, 18H), 1.75 (m, 2H), 2.85 (m,2H), 3.75 (m, 1H), 4.00 (m, 1H) and 6.20 (m, 2H).

HRMS exact mass calculated for C₁₇ H₃₁ O₄ S (M+H)⁺ 331.1943, found331.1947.

4-(Dodecylsulfonylmethyl)-5-hydroxy-2(5H)-furanone

Oxidizing 4-dodecylthiomethyl-2-triethylsilylfuran with potassiumperoxymonosulfate gives 4-dodecylsulfonylmethyl-2-triethylsilylfuran.Treatment of this intermediate with singlet oxygen and using Rose Bengalas initiator gives the title compound.

EXAMPLE 10 (E)(Z)-Methyl 3-{2-triethylsilyl-4-furyl)propen-2-oate(Compound 10) and (E)(Z) Methyl3-(2-trimethylsilyl-4-furyl)propen-2-oate

Compound 10 and the corresponding trimethylsilyl derivative are preparedas described above in EXAMPLE 5.

3-(2-triethylsilyl-4-furyl)propan-1-ol and3-(2-trimethylsilyl-4-furyl)propan-1-ol

These compounds are prepared as described above in EXAMPLE 5.

3-(2-Trimethylsilyl-4-furyl)propyl dodecanoate

Pyridine (0.06 ml, 0.72 mmol) was added to a mixture of3-(5-trimethylsilyl-3-furyl)propan-1-ol (from above) and lauroylchloride (0.17 ml, 0.72 mmol) in tetrahydrofuran (4 ml) at roomtemperature. After 14 hours, the mixture was diluted with ether (10 ml)and washed successively with water, copper (II) sulphate and brine.Evaporation of the dried (magnesium sulphate) organic layers gave anoil, which was purified by preparative TLC (20×20 cm, 500u silica plate;developed with 10% ethyl ether/petroleum ether). The title ester wasobtained as a colorless oil.

¹ H NMR (CDCl₃): 0.28 (s, 9H), 0.92 (t, 3H, J=7.3 Hz), 1.29 (brs, 18H),1.65 (m, 2H), 1.92 (p, 2H, J=7.4 Hz), 2.33 (m, 2H), 2.53 (t, 2H, J=7.9Hz), 4.13 (m, 2H), 6.53 (s, 1H) and 7.45 (s, 1H).

MS m/e (% abundance): 381 (M⁺ +1, 13), 365 (4), 183 (29), 180 (100), 154(33), 101 (52) and 73 (64).

4-(3-Dodecanoyloxypropyl)-5-hydroxy-2(5H) furanone(Compound 50)

A mixture of 3-(5-trimethylsilyl-3-furyl)propyl dodecanoate (105 mg,0.27 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (6 ml) was exposedto singlet oxygen for 2.5 hours at -78 degrees. The residue, aftersolvent removal, was purified by preparative thin layer chromatography(TLC) (20×20 cm, 500u silica plate; developed with 60% ethylether/petroleum ether). The title ester was obtained as an off-whitesolid.

¹ H NMR (COCl₃): 0.89 (t, 3H, J=6.9 Hz), 1.27 (brs, 18H), 1.60 (m, 2H),1.99 (p, 2H, J=7.4 Hz), 2.32 (t, 2H, J=7.7 Hz), 2.52 (brt, 2H), 4.17 (t,2H, J=6.3 Hz), 5.91 (s, 1H), and 6.03 (s, 1H).

¹³ C NMR (CDCl₃): 14.1, 22.7, 24.3, 24.9, 25.8, 29.1, 29.3, 29.5, 29.6,31.9, 34.3, 63.1, 99.2, 117.8, 168.6, 171.3 and 174.3.

MS m/e: Exact mass calculated for C₁₉ H₃₆ NO₅ (M+NH₄)⁺ 358.2593, found358.2583.

Octyl 3-(2-trimethylsilyl-4-furyl)propen-2-oate (Compound 11), and Octyl3-(5-hydroxy-2-on-4-furyl)propen-2-oate (Compound 51)

Lithium diisopropylamide (a 1.5 M solution in cyclohexane; 1.34 ml, 2.0mmol) was added dropwise to a solution of octyl acetate (322.2 mg, 193mmol) in tetrahydrofuran (7 ml) at -78 degrees under argon. After 20minutes, a solution of 5-trimethylsilyl-3-furaldehyde (324 mg, 1.93mmol) in tetrahydrofuran (1 ml) was added. Stirring was continued at -78degrees for I hour and trifluoromethanesulfonic anhydride (0.65 ml, 3.86mmol) was added. After 1 hour, 1,8-diazobicyclo[5.4.0]undec-7-ene (0.58ml, 3.86 mmol) was added and stirring was continued overnight while thecooling bath attained room temperature. The mixture was diluted withether (30 ml) and acidified with diluted HCl. Extraction (ethyl ether),washing of the extracts (brine), drying (magnesium sulphate) andevaporation afforded an oil, which was subjected to flash chromatography(silica). Elution with 10% ethyl ether/hexane gave octyl3-(2-trimethylsilyl-4-furyl) propen-2-oate (Compound 11) as a lightyellow oil, and oxidation with singlet oxygen gave octyl3-(5-hydroxy-2-on-4-furyl)propen-2-oate (Compound 51).

Compound 11: ¹ H NMR (CDCl₃): 0.29 (s, 9H), 0.91 (t, 3H, J=6.9 Hz), 1.30(brs, 10H), 1.70 (m, 2H), 4.18 (t, 2H, J=6.8 Hz) 6 17 (d, 1H, J=I5.0Hz), 6.80 (s, 1H), 7.60 (d, 1H, J=15.6 Hz), and 7.84 (s, 1H).

MS m/e (%abundance): 323 (M⁺ +1, 20), 322 (m⁺, 47), 307 (15), 210 (36),195 (61), 166 (70) and 73 (100).

EXAMPLE 11 5-Methyl-2-trimethylsilyl-4-furaldehyde

n-Butyl lithium (a 1.6 M solution in hexane; 2.04 ml, 3.28 mmol) wasadded dropwise to a solution of N,N'N'-trimethylethylenediamine (0.46ml, 3.56 mmol) in tetrahydrofuran (7 ml) at -78 degrees under argon.After 15 minutes, a solution of 2-trimethylsilyl-4-furaldehyde (0.5 g,2.98 mmol) in tetrahydrofuran (2 ml) was added, followed by n-butyllithium (3.72 ml, 5.94 mmol) after 15 minutes. Iodomethane (1.12 ml,17.9 mmol) was then added and the mixture was allowed to warm to roomtemperature gradually over 1/2 hour. The mixture was quenched with brineand extracted with ethyl ether. Evaporation of the dried (magnesiumsulphate) extracts gave an oil, which was purified by flashchromatography using 10% ethyl ether/hexane. Fractions with R_(f) ofabout 0.22 on evaporation afforded the title methylfuran as a lightyellow oil.

¹ H NMR (CDCl₃) 0.29 (s, 9H), 2.63 (s, 3H), 6.91 (s, 1H) and 9.95 (s,1H).

LRMS m/e (% abundance) 183 (M⁺ +1, 35), 167 (28), 149 (20), 83 (40), 73(100) and 43 (31).

5-Methyl-4-(1-acetoxytridecyl)-2-trimethylsilylfuran

A mixture of 1-bromododecane (261 mg, 0.11 mmol) and magnesium turnings(27 mg, 0.11 mmol) in tetrahydrofuran (7 ml) was refluxed under argonfor 1 hour. After cooling to room temperature, a solution of5-methyl-2-trimethylsilyl-4-furaldehyde (158.6 mg, 0.87 mmol) intetrahydrofuran (1 ml) was added, followed by acetic anhydride (0.25 ml,2.6 mmol) after 1 hour. Stirring was continued at room temperatureovernight and the mixture was quenched with water. Extraction (ethylether) and evaporation of the dried (magnesium sulphate) extracts gavean oil, which was purified by preparative TLC (20×20 cm, 1000 micronsilica plate; developed with 5% ethyl ether/hexane). The title ester wasobtained as a light yellow oil.

¹ H NMR (CDCl₃) 0.26 (s, 9H), 0.91 (t, 3H, J=6.9 Hz), 1.27 (,s 20H),1.60-1.90 (m, 2H), 2.05 (s, 3H), 2.35 (s, 3H), 5.69 (t, 1H, J=7.5 Hz)and 6.55 (s, 1H).

LRMS m/e (% abundance) 394 (M⁺, 8), 352 (23), 334 (36), 83 (47), 167(20), 117 (28), 73 (I00) and 43 (41).

4-(1-Acetoxytridecyl)-5-hydroxy-5-methyl-2-furanone(Compound 60)

A mixture of 5-methyl-4-(1-acetoxytridecyl)-2-trimethylsilylfuran (237mg, 0.60 mmol) and Rose Bengal (5 mg) in tetrahydrofuran (10 ml) wasexposed to singlet oxygen at -78 degrees C. for 2 hours. The residue,after solvent removal, was purified by preparative TLC (20×20 cm, 1000micron silica plate; developed with 60% ethyl ether/hexane). The titlefuranone was obtained as a light yellow oil. This compound is a mixtureof epimers which isomerizes upon standing.

¹ H NMR (CDCl₃) 0.92 (t, 3H, J=6.9 Hz), 1.30 (brs, 20H), 1.70 (brs, 3H),1.80 (m, 2H), 2.15 (2s, 3H), 5.25 (brm, 1H), 5.45 (t, 0.7H, J=7.5 Hz),5.96 (s, .7H), 6.03 (s, 0.3H) and 6.11 (brm, 0.3H).

¹³ C NMR (CDCl₃) 13.7, 20.5, 22.3, 23.3, 24.1, 24.9, 28.8, 29.0, 29.1,29.2, 29.3, 31.6, 33.2, 33.3, 69.0, 69.3, 106.5, 117.0, 118.1, 169.6,169.7, 169.8, 170.0, 170.1, 170.7, 171.9 and 172.0.

HRMS exact mass calculated for C₂₀ H₃₈ NO₅ (M+NH₄)⁺ 372.2749, found372.2754.

3-(O-tert-Butyldimethylsilylmethoxy)furan

3-Furylmethanol (15.5 ml, 0.18 mol), followed by1,8-diazabicyclo[5.4.0]undec-7-ene (29.7 ml, 0.19 mol) was added to asolution of tert-butyldimethylsilyl chloride (29.9 g, 0.19 m) indichloromethane (140 ml) at 0 degrees C. under argon. After stirring atroom temperature overnight, the reaction was quenched with 5% ice coldhydrochloric acid. Extraction with dichloromethane and evaporation ofthe dried (magnesium sulfate) extracts gave an oil which was purified byflash chromatography on silica using hexane to give the desired silylether. (See Reference: Patrick G. Spinazze and Brian A Keay, "THE 1,4C-O SILYL MIGRATIONS OF VARIOUS FURAN AND THIOPHENE SYSTEMS",Tetrahedron Letters., Vol. 30, No. 14, pp 1765-1768, 1989).

¹ H NMR (CDCl₃): 0.05 (s, 6H), 0.89 (s, 9H), 4.58 (s, 2H), 6.35 (1H) and7.33 (m, 2H).

3-(2-tert-Butyldimethylsilyl)furylmethanol

n-BuLi (a 1.5 M solution in hexane; 38.9 ml, 58 mmol) was added to asolution of 3-(O-tert-butyldimethylsilylmethoxy)furan (11.2 g, 52.7mmol) and hexamethylphosphoramide(10.1 ml, 58 mmol) in tetrahydrofuran(200 ml) at -78 degrees C. under argon. After 1 hour stirring at -20degrees C., the reaction was quenched with an aqueous solution ofsaturated ammonium chloride. Extraction (ethyl acetate) and evaporationof the dried (magnesium sulfate) extracts gave an oil, which waspurified by flash chromatography on silica using 20% ethylacetate/hexaneto give the desired furylmethanol.

¹ H NMR (CDCl₃): 0.29 (s, 6H), 0.90 (s, 9H), 1.45 (brt, 1H), 4.59 (d,2H, J=3.4 Hz), 6.49 (d, 1H, J-1.7 Hz) and 7.60 (d, 1H, J=1.7 Hz).

2-(tert-Butyldimethylsilyl)-3-hydroxymethyl-4-furaldehyde

n-BuLi (a 1.6 M solution in hexane; 2.7 ml, 4.28 mmol) was addeddropwise to a solution of 3-(2-tert-butyldimethylsilyl)-furylmethanol(430 mg, 2.0 mmol) in dimethoxyethane (5 ml) at -78 degrees C. underargon. After stirring at 0 degrees c for 15 minutes, lithium chloride(860 mg, 20.4 mmol), followed by N,N-dimethylformamide (0.35 ml, 4.48mmol) was added. Stirring continued at 0 degrees C. for 16 hours and themixture was quenched with ammonium chloride. Extraction with ethylacetate and evaporation of the dried (magnesium sulfate) extracts gave asolid, which was recrystallized from hexane to

IR (CHCl₃) 3470, 1680, 1660, 1570 and 1510.

¹ H NMR (CDCl₃) 0.28 (s, 6H), 0.87 (s, 9H), 4.08 (t, 1H, J =7.3Hz), 4.58(d, 2H, J=7.3 Hz), 8.27 (s, 1H) and 9.90 (s, 1H).

¹³ CNMR (CDCl₃) 5.9, 17.1, 26.1, 55.4, 128.3, 133.9, 158.2, 158.3 and186.6.

LRMS m/e (% abundance 0.258 [(M+NH₄)⁺, 1], 240 (56), 223 (53), 184 (26),183 (10) and 167 (41).

4-2-(tert-Butyldimethylsilyl)-3-methyl]furylmethanol

a) 3-(2-tert-Butyldimethylsilyl-4-carbonyl)furylmethyl methanesulfonate

A solution of 2-(tert-butyldimethylsilyl)-3-hydroxymethyl-4-furaldehyde(4.98 g, 20.7 mmol), diisopropylethylamine (7.95 ml, 45.6 mmol) intetrahydrofuran (70 ml) was added dropwise to a solution ofmethanesulfonyl chloride (6.42 ml, 82.9 mmol) in tetrahydrofuran (70 ml)at -20 degrees C. under argon. After stirring at -20 degrees C. for 90minutes, the mixture was diluted with ethyl ether and washedsuccessively with 10% hydrochloric acid, water and brine. Evaporation ofthe dried (magnesium sulfate) organic phase gave an oil, which waspurified by flash chromatography on silica using 20% ethylacetate/hexaneto give the titled mesylate.

¹ HNMR (CDCl₃) 0.36 (s, 6H), 0.93 (s, 9H), 3.16 (s, 3H), 5.33 (s, 2H),7.27 (s, 1H), 8.26 (s, 1H) and 10.02 (s, 1H).

b) 4-2-(tert-Butyldimethylsilyl)-3-methyl]furylmethanol

Lithium aluminum hydride (a 1.0 M solution in THF; 62.2 ml, 62.2 mmol)was added dropwise to a solution of the mesylate from above in THF (10ml) at -20 degrees C. under argon. After 20 minutes, TLC showed that thereaction has been completed. The mixture was quenched carefully withdilutehydrochloric acid. Extraction with ethyl ether and evaporation ofthe dried (magnesium sulfate) extracts gave an oil, which was purifiedby flash chromatography on silica using 20% ethyl acetate/hexane to givethe titled alcohol.

IR (CHCl₃) 3450 and 1600

¹ HNMR (CDCl₃) 0.27 (s, 6H), 0.91 (s, 9H), 2.12 (s, 3H), 4.53 (s, 2H)and 7.56 (s, 1H).

¹³ CNMR (CDCl₃) -6.1, 9.0, 17.5, 26.2, 55.4, 125.5, 130.8, 144.6 and155.1

LRMS m/e (% abundance) 226 (M⁺, 32), 209 (45), 170 (18), 169 (91), 142(13), 141 (100), 101 (10) 97 (41), 75 (93) and 73 (22).

2-(tert-Butyldimethylsilyl)-3-methyl-4-furaldehyde

A solution of 4-[2-(tert-butyldimethylsilyl)-3-methyl]furyl-methanol(380 mg, 1.68 mmol) in dichloromethane (5 ml) was added to a suspensionof barium permanganate (6.45 g, 25.2 mmol) in dichloromethane (40 ml) at0 degrees C. under argon. After stirring at room temperature for 15hours, the mixture was filtered through celite. After concentration byon silica using 5% ethyl ether/hexane to give the titled aldehyde.

IR (CHCl₃) 2820, 2740 and 1680

'HNMR (CDCl₃) 0.2 (s, 6H), 0.82 (s, 9H), 2.23 (s, 3H), 8.09 (s, 1H) and9.91 (s, 1H).

¹³ CNMR (CDCl₃) -6.3, 9.8, 17.3, 25.9, 128.1, 129.9, 156.8, 157.6 and185.7.

LRMS m/e (% abundance) 224 (11), 168 (16), 167 (I00), 83 (12) and 73(11).

4-(1-Acetoxytridecyl)-2-(tert-butyldimethylsilyl)-3-methylfuran

2-(tert-Butyldimethylsilyl)-3-methyl-4-furaldehyde (95 mg, 0.42 mmol)was added to a solution of dodecylmagnesium bromide (a 1.0 M solution inTHF; 0.51 ml, 0.51 mmol) in THF (1 ml) at 0 degrees C. under argon. Whenall the aldehyde has reacted, acetic anhydride (80 microliter, 0.85mmol) was added. After stirring at room temperature for 16 hours, themixture was quenched with dilute hydrochloric acid. Extraction withdiethyl ether and evaporation of the dried (magnesium sulfate) extractsgave an oil, which was purified by flash chromatography on silica using5% ethyl ether/hexane to give the titled acetate.

IR (CHCl₃) 1730 and 1710.

'HNMR (CDCl₃) 0.26 (s, 6H), 0.88 (t, 3H, J =6.9 Hz), 1.25 (brs, 20H),1.80 (m, 2H), 2.03 (s, 3H), 2.07 (s, 3H), 5.78 (t, 1H, J=7.0 Hz) and7.52 (s, 1H)

¹³ CNMR (CDCl₃) -6.1, 9.5, 13.8, 17.5, 21.0, 22.5, 25.4, 26.2, 29.1,29.2, 29.3, 29.4, 31.7, 34.6, 68.4, 125.4, 130.2, 144.4, 154.7 and 170.7

LRMS m/e (% abundance) 436(M⁺, 4), 320 (3), 211 (14), 118 (10), 117(100), 75 (22) and 73 (18).4-(1-Acetoxytridecyl)-3-methyl-5-hydroxy-2(5H)-furanone (Compound 61)

A mixture of 4-(1-acetoxytridecyl)-2-tert-butyldimethylsing3-methylfuran (132 mg, 0.3 mmol), water (a few drops) and Rose Bengal(5mg) in acetone (30 ml) was exposed to singlet oxygen at 0 degrees C.for 6 hours. The residue, on evaporation, was purified by flashchromatography on silica using 20% ethylacetate/hexane to give thetitled furanone as a mixture of stereoisomers.

'H NMR (CDCl₃) 0.82 (t, 3H, J=6.9 Hz), 1.20 (brs, 20H), 1.75 (m, 2H),1.85 (s, 3H), 2.03 (s, 3H), 2.06 (s, 3H), 5.35 9m, 2H), 5.88 (brs, 1H)and 6.08 (brs, 1H).

¹³ C NMR (CDCl₃) 9.2, 14.2, 20.8, 22.8, 25.6, 29.4, 29.5, 29.6, 29.7,29.8, 32.1, 32.8, 70.1, 70.7, 97.7, 128.5, 128.9, 156.5, 156.6, 171.7,172.1, 172.7 and 173.1.

LRMS m/e (% abundance) 355 (M⁺, 16), 296 (11), 295 (59), 294 (100), 277(19), 267 (45), 126 (34), 125 (41), 112 (18), 95 (23), 81 (22) and 69(27).

2-(tert-butyldimethylsily)-3-methyl-4-(1-phenylcarbamoyloxy)tridecylfuranand2-(tert-butyldimethylsily)-3-methyl-4-[1-N-phenyl-N-phenylcarbamoyl)carbamoyloxy]tridecylfuran

Dodecylmagnesium bromide (a 1.0 M solution in THF; 0.89 ml, 0.89 mmol)was added to a solution of2-tert-butyldimethylsilyl-3-methyl-4-furaldehyde (200 mg, 0.89 mmol) inTHF (5 ml) at 0 degrees C. under argon. After stirring at roomtemperature for 1 hour, the mixture was recooled to 0 degrees C. andphenylisocyanate (97 microliter, 0.89 mmol) was added. Stirring wascontinued for 5 minutes and the reaction mixture was quenched withammonium chloride. Extraction with diethyl ether and evaporation of thedried (magnesium sulfate) extracts gave an oil. The crude product waspurified by flash chromatography (SiO₂ ; 5% diethylether/hexane) to givethe desired mono- and bis-phenylcarbonate.2-(tert-Butyldimethylsilyl)-3-methyl-4-(1-phenylcarbamoyloxy)tridecylfuran:R_(f) (5% diethyl ether/hexane) 0.34; IR (CHCl₃) 3430, 1725, 1680, 1595and 1515; 'HNMR (CDCl₃) 0.24 (s, 6H), 0.88 (t+s, 12H), 1.23 (m, 20H),1.90 (m, 2H), 2.09 (s, 3H), 5.77 (t, 1H,J =7.0 Hz), 6.65 (s, 1H), 7.02(t, 1 H, J=7.3 Hz), 7.25 (m, 2H), 7.35 (m, 2H) and 7.54 (s, 1H); ¹³ CNMR(CDCl₃) -6.1, 9.6, 13.8, 17.5, 22.4, 25.4, 26.2, 29.1, 29.2, 29.3, 29.4,31.7, 34.8, 69.5, 118.7, 123.5, 125.4, 129.2, 130.2, 138.2, 144.4, 153.4and 154.9.

2-(tert-Butyldimethylsilyl)-3-methyl4-[1-(N-phenyl-N-phenylcarbamoyl)carbamoyloxy]tridecylfuran: R_(f) (5%diethyl ether/hexane) 0.23; 'H NMR (CDCl₃) 0.24 (s, 6H), 0.87 (s+t,12H), 1.24 (m, 20H), 1.56 (m, 2H), 1.79 (s, 3H), 5.75 (t, 1H, J=6, 2Hz),7.07 (t, 1H, J-8.0 Hz), 7.20 (m, 2H), 7.30 (m, 3H), 7.42 (m, 3H), 7.54(m, 2H) and 10.9 (s, 1H); ¹³ CNMR (CDCl₃)-6.2, -6.1, 9.3, 13.6, 17.5,22.4, 24.9, 26.1, 28.8, 29.1, 29.2, 29.3, 29.4, 31.7, 34.4, 72.8, 120.0,124.0, 124.1, 128.4, 128.9, 129.0, 129.5, 137.4, 138.0, 144.3, 151.8,155.3 and 155.6.

5-Hydroxy-3-methyl-4-(1-phenylcarbamoyloxy)tridecyl)2(5H)furanone

A mixture of2-(tert-butyldimethylsilyl)-3-methyl-4-(1phenylcarbamoyloxy)tridecylfuran(226 mg, 0.44 mmol), water (a few drops) and polymer bound Rose Bengal(.077 g) in acetone (80 ml) was exposed to singlet oxygen at 0 degreesC. for 5 hours The residue, on evaporation, was purified by flashchromatography (SiO₂, 20% ethylacetate/hexane) to give the titledfuranone as a mixture of stereoisomers. IR (CHCl₃) 3400-3200, 1768,1725, 1605 and 1520; 'HNMR (CDCl₃) 0.88 (t, 3H, J=6.9 Hz), 1.26 (m,20H), 1.80 (m, 1H), 1.91 (s, 3H), 1.95 (m, 1H), 5.48 (brt, 1H), 5.52 (m,1H), 5.95 (br, 1H), 6.04 (brs, 1H), 6.19 (brs, 1H), 7.00-7.40 (m, 6H);¹³ C NMR (CDCl₃) 8.7, 13.8, 22.4, 25.2, 28.9, 29.1, 29.2, 29.3, 29.4,29.5, 31.7, 32.4, 32.5, 69.9, 70.6, 97.2, 97.4, 118.8, 119.0, 119.4,123.9, 124.1, 128.1, 128.9, 129.2, 137.3, 137.6, 153.2, 153.4, 153.6,156.0, 156.8, 172.5 and 172.7.

5-Methyl-2-triethylsilyl-4-furaldehyde

n-Butyl lithium (a 1.6 M solution in THF; 19.0 ml, 30.4 mmol) was addedto a solution of morpholine (2.67 ml, 30.4 mmol) in THF (20 ml) at -78degrees C. under argon. After 20 minutes, 3-furaldehyde (1.8 ml, 28.9mmol) was added, followed by s-butyl-lithium (a 1.3 M solution incyclohexane; 23.4 ml, 30.4 mmol) after another 20 minutes. Stirring wascontinued for 2 hours and chlorotriethylsilane (5.1 ml, 30.4 mmol) wasadded. After 2 hours at -78 degrees C., s Buli (23.4 ml, 30.4 mmol) wasadded, followed by iodomethane (5.4 ml, 86.9 mmol) after another 2hours. The mixture was stirred at room temperature for 15 hours andquenched with ice cold dilute hydrochloric acid. Extraction with ethylether and evaporation of the dried (magnesium sulfate) extracts gave anoil, which was purified by flash chromatography on silica using 10%diethyl ether/hexane to give the titled aldehyde.

IR (CHCl₃) 1690

'HNMR (CDCl₃) 0.75 (q, 6H, J=8.0 Hz), 0.98 (t, 9H, J=8.0 Hz), 2.60 (s,3H), 6.90 (s, 1H) and 9.90 (s, 1H).

¹³ CNMR (CDCl₃) 2.6, 6.7, 12.5, 118.8, 122.8, 158.5, 166.2 and 185.1;HRMS exact mass calculated for C₁₂ H₂₀ O₂ Si 224.1232 found 224.1226

4-(1-Acetoxytridecyl)-5-methyl-2-triethylsilylfuran

5-Methyl-2-triethylsilyl-4-furaldehyde (145 mg, 0.65 mmol) was added toa solution of dodecylmagnesium bromide (a 1.0 M solution in THF; 0.76ml, 0.74 mmol) in THF at 0 degrees C. under argon. When all the aldehydehas consumed, acetic anhydride (0.1 6 ml, 1.71 mmol) Was added. StirringWas continued at room temperature for I5 hours and the mixture wasquenched with water. Extraction with diethyl ether and evaporation ofthe dried (magnesium sulfate) extracts gave an oil, which was purifiedby flash chromatography on silica using 5% diethylether/hexane to givethe titled acetate.

IR (CHCl₃) 1730

'HNMR (CDCl₃) 0.75 (q, 6H, J=8.0 Hz), 0.88 (t, 3H, J=7.0 Hz), 0.95 (t,9H, J=8.0 Hz), 1.25 (brs, 20H), 1.75 (m, 1H), 1.95 (m, 1H), 2.01 (s,3H), 2.31 (s, 3H), 5.69 (t, 1H, J =7.2 Hz) and 6.55 (s, 1H).

¹³ CNMR (CDCl₃) -2.9, 7.0, 11.9, 13 8, 21.0, 22.5, 25.3, 25.7, 29.0,29.2, 29.3, 29.4, 31.7, 34.8, 68.8, 118.8, 120.3, 154.1, 156.1 and170.7. LRMS m/e (% abundance) 436 (M⁺, 9), 377 (22), 376 (33), 347 (43),239 (29), 145 (100), 115 (34), 103 (30) AND 87 (30); HRMS Exact Masscalculated for C₂₆ H₄₈₀₃ Si (M⁺) 43 6.3373, found 436.3374.

4-(1-Acetoxytridecyl)-5-hydroxy-5-methyl-2-furanone(Compound 60)

A mixture of 4-(1-acetoxytridecyl)-2-methyl-5-triethylsilylfuran (231mg, 0.53 mmol), water (a few drops) and Rose Bengal (6.3 mg) in acetone(100 ml) was exposed to singlet oxygen at 0 degrees C. for 3 hours. Theresidue, after evaporation, was purified by flash chromatography onsilica using 10% ethylacetate/hence to give the titled furanone. Thiscompound is a mixture of epimers which isomerizes upon standing.

IR (CHCl₃) 3600-3200, 1770 and 1740. For other physical data of thiscompound see description of the same above.

5-Methyl-2-triethylsilyl-4-(1-phenylcarbamoyloxy)tridecylfuran

A solution of 5-methyl-2-triethylsilyl-4-furaldehyde (219 mg, 0.98 mmol)in THF (5 ml) was added to a solution of dodecylmagnesium bromide (a 1.0M solution in THF; 1.08 ml; 1.08 mmol) in THF at 0 degrees C. underargon. When all the aldehyde was consumed, phenylisocyanate (0.12 ml,1.08 mmol) was added. After stirring at room temperature for 16 hours,the mixture was quenched with dilute hydrochloric acid. Extraction withdiethylether and evaporation of the dried (magnesium sulfate) extractsgave an oil, which was purified by flash chromatography on silica using5% ethyl ether/hexane to give the titled furan.

IR (CHCl₃) 3440, 1730 and 1520.

'HNMR (CDCl₃) 0.72 (q, 6H, J=6.6 Hz), 0.88 (t, 3H, J=6.6 Hz), 0.98 (t,9H, J=6.6 (Hz), 1.25 (brs, 20H), 1.75 (m, 1H), 1.95 (m, 1H), 2.36 (s,3H), 5.70 (t, 1H, J-7.3 Hz), 6.57 (s, 1H), 6.62 (br, 1H), 7.02 (m, 1H),7.29 (m, 2H) and 7.37 (m, 2H).

¹³ CNMR (CDCl₃) 2.9, 7.1 11.9, 13.8, 22.5, 25.3, 29.1, 29.2, 29.3, 29.4,31.7, 35.0, 69.9, 118.7, 118.8, 120.2, 123.3, 129.1, 138.3, 144.8,153.5, 154.3 and 156.3.

5-Methyl-5-hydroxy-4-(1-phenylcarbamoyloxy)tridecyl-2-furanone (Compound62)

A mixture of 5-methyl-2-triethylsilyl-4-(1phenylcarbamoyloxy)tridecylfuran (80 mg, 0.13 mmol) water (a few drops) and Rose Bengal(ca, 3 mg) in acetone (60 ml) was exposed to singlet oxygen at 0 degreesC. for 4 hours. The residue, after evaporation, was purified by flashchromatography on silica using 20% ethylacetate/hexane to give thetitled furanone.

IR (CHCl₃) 3440, 3400-3240, 1765, 1730, 1600 and 1525.

'HNMR (CDCl₃) 0.88 (t, 3H, J-6.9 Hz), 1.26 (brs, 20H), 1.67 (brm, 2H),1.79 (brs, 3H), 5.18 (brm, 1H), 5.50 (brm, 1H), 5.85 (br, 1H), 6.03 (br,1H), 7.12 (m, 2H) and 7.40 (m, 3H).

¹³ CNMR (CDCl₃) 13.8, 22.4, 22.8, 24.2, 24.3, 24.8, 25.1, 28.9, 29.1,29.2, 29.3, 29.4, 31.7, 3.33, 34.0, 69.6, 70.2, 70.3, 98.2, 106.5,118.1, 119.2, 124.1, 124.3, 124.5, 129.3, 136.9, 153.9, 169.9 and 170.4.

LRMS m/e (% abundance) 431 (M⁺, 4), 277 (7), 153 (6), 137 (12), 126(12), 119 (25), 109 (11), 94 (13), 93 (100) and 55 (30).

5-Butyl-2-triethylsilyl-4-furaldehyde

Using the same procedure as 5-methyl-2-trimethylsilyl-4-furaldehyde butsubstituting 2-trimethylsilyl-4-furaldehyde and methyl iodide with2-triethylsilyl-4-furaldehyde and 1-iodobutane respectively gives5-butyl-2-triethylsilyl-4-furaldehyde. IR (neat) 1690 cm⁻¹ ; 'HNMR(CDCl₃) 0.73 (q, 65H, J=8.4 Hz), 0.95 (m, 12H), 1.36 (p, 2H, J=7.5 Hz),1.69 (p, 2H, J=7.5 Hz), 2.94 (t, 2H, J=7.5 Hz), 6.89 (s, 1H) and 9.91(s, 1H) ¹³ CNMR (CDCl₃): 3.03, 7.17, 13.6, 22.2, 26.8, 30.4, 118.6,122.5 158.4, 170.2 and 184.8. LRMS m/e (% abundance) 266 (M⁺, 20) 238(20) 237 (100), 87 (10) and 75 (20); HRMS exact mass calculated for C₁₅H₂₆ O₂ Si 266.1702, found 266.1690.

5-Butyl-5-hydroxy-4-(1-phenylcarbamoyloxy)tridecyl-2-furanone

a) 5-Butyl-4-(1-phenylcarbamoyloxy)tridecyl-2triethylsilylfuran

Dodecyl magnesium bromide (a 1.0 M solution in THF; 0.25 ml, 0.25 mmol)was added to a solution of 5-butyl-2-triethylsilyl-4-furaldehyde (59 mg,0.22 mmol) in THF (1 ml) at 0 degrees C. under argon. When all thealdehyde has reacted, phenylisocyanate (27 microliter, 0.25 mmol) wasadded and stirring was continued at -40 degrees C. for 14 hours. Withoutpurification the crude product was used in the next step.

'HNMR (CDCl₃)

b) 5-Butyl-5-hydroxy-4-(1-phenylcarbamoyloxy)tridecyl-2furanone

Water (a few drops) and Rose Bengal (ca. 3 mg) were added to the abovereaction mixture. The mixture was exposed to singlet oxygen for 3 hoursat 0 degrees C. The residue, after evaporation, was purified bypreparative TLC (S_(i) O₂) developed with 40% diethyether/hexane to givethe titled furanone. IR (CHCl₃) 3600-3240, 3440, 1770, 1760, 1730, 1605,1550, and 1530. 'HNMR (CDCl₃) 0.88 (m, 6H), 1.30 (brm, 22H), 1.50 (m,2H), 1.75 (m, 2H), 2.00 (m, 2H), 5.10 (brm, 1H), 5.70 (br, 1H), 6.04(brs, 1H), 6.95 (brs, 1H), 7.15 (brm, 1H), 7.30 (m, 3H) and 7.50 (m, 2H)

¹³ C NMR (CDCl₃) 13.6, 13.8, 22.1, 2.22, 22.4, 24.3, 24.6, 25.1, 28.6,28.9, 29.0, 29.1, 29.3, 29.4, 31.7, 32.9, 33.5, 36.3, 69.7, 108.3,118.9, 119.2, 119.4, 120.2, 124.5, 128.6, 129.0, 129.2, 129.3, 129.4,136.8, 169.2, 169.7 and 169.9.

LRMS m/e (% abundance) 491[(M+NH₄)⁺, 67], 474[(M+H)⁺, 86], 473 (M⁺, 23),456 (33), 372 (30), 354 (30), 337 (66), 319 (38), 272 (48), 213 (80),120 (27) 119 (45), 94 (58) and 93 (100).

2-tert-Butyldimethylsilyl-3,5-dimethy-4-furaldehyde

Treatment of 2-tert-butyldimethylsilyl-4-hydroxymethyl-3-methylfuranwith n-butyl lithium and iodomethane gives2-tert-butyldimethylsilyl-3,5-dimethyl-4-hydroxymethylfuran. Oxidizingof this furan with barium permanganate gives the titled furaldehyde.

2-Triethylsilyl-5-phenyl-4-furaldehyde.

Treatment of 2-triethylsilyl-4-furaldehyde with lithioN,N,N'-trimethylethylenediamine, followed by phenyltrifluoromethanesulfonate in the presence of anhydrous zinc chloride andtetrakis (triphenylphosphine) palladium (o) and work up gives the titledaldehyde.

3-Phenyl-2-triethylsilyl-4-furaldehyde

n-Butyllithium (a 1.42 M solution in hexane, 2.33 ml, 3.31 mmol) wasadded to a solution of 1-methylpiperazine (331 mg. 3.31 mmol) intetrahydrofuran (15 ml) at 0 degrees under argon. After 15 minutes thesolution was cooled to -78 degrees and 4-phenyl-3-furaldehyde. (517 mg,3.01 mmol) was added. This mixture was warmed to 0 degrees and stirredfor 15 minutes, then recooled to -78 degrees before sec-butyllithium (a1.3 M solution in cyclohexane, 2.77 ml, 3.61 mmol) was added dropwise.This solution was stirred 12 hours at -78 degrees C. beforechlorotriethylsilane (1.81 g, 12.02 mmol) was added. The mixture wasallowed to warm gradually to room temperature and stirred an additional11/2 hours. The reaction was quenched with ice-cold 5% (V/V)hydrochloric acid and the organics were extracted into ethyl ether. Thecombined fractions were washed with saturated sodium bicarbonate, H₂ Oand brine. Evaporation of the dried (magnesium sulfate) extracts gave anoil which was purified by flash chromatography on silica using 10% ethylacetate/hexanes to give the title aldehyde.

IR (heat): 2952, 1691 cm:

¹ H NMR (CDCl₃): 0.62 (q, J=7.8 Hz, 6H); 0.85 (t, J=7.8 Hz, 9H); 7.20 to7.43 (m, 5H); 8.30 (s, 1H); 9.79 (s, 1H).

¹³ C NMR (CDCl₃): 3.0, 6.8, 127.1, 128.2, 130.2, 131.8, 136 5, 153.7,158.3, 186.1.

3-phenyl-2-triethylsilyl-4-furanmethanol

LiAlH₄ (1.0 M solution in hexane, 1.48 ml, 1.48 mmol) was added dropwiseto a solution of 3-phenyl-2-triethylsilyl-4furaldehyde (422 mg, 1.48mmol) in tetrahydrofuran (10 ml) at 0 degrees under argon. This mixturewas warmed to room temperature, quenched with ice-cold 5% (V/V)hydrochloric acid and the organics were extracted into ethyl ether. Thecombined fractions were washed with saturated sodium bicarbonate, H₂ Oand brine. The dried extracts (magnesium sulfate) were concentrated toan oil which was purified by flash chromatography on silica using 20%ethyl acetate/hexanes to give the title compound. IR (neat): 3300(broad); 2953 cm⁻¹.

¹ H NMR (CDCl₃): 0.59 (q, J=8.0 Hz, 6H); 0.85 (t, J=8.0 Hz, 9H);1.60(brs, 1H); 4.42 (brs, 2H); 7.29 to 7.40 (m, 5H); 7.68 (s, 1H).

¹³ C NMR (CDCl₃) 3.2, 6.9, 55.2, 125.2, 127.6, 128.2, 130.0, 133.7,137.5, 144.9, 155.7.

4-Dodecoyloxymethyl-3-phenyl-2-triethylsilylfuran

To a stirred solution of 3-phenyl-2-triethylsilyl-4-furanmethanol (345mg, 1.20 mmol) and triethylamine (182 mg, 1.80 mmol) in tetrahydrofuran(15 ml) at 0 degrees under argon was added lauroyl chloride (786 mg,3.60 mmol). This solution was allowed to warm gradually to roomtemperature. After stirring an additional 2 hours the white precipitatewas filtered off. The filtrate was taken up into ethyl ether, washedwith saturated ammonium chloride, saturated sodium bicarbonate, H₂ O andbrine. Evaporation of the dried (magnesium sulfate) extracts gave an oilwhich was purified by flash chromatography on silica using 2% ethylether/hexanes to give the title compound.

IR (neat): 1737 cm⁻¹.

¹ H NMR (CDCl₃): 0.60 (q, J=8.1 Hz, 6H); 0.81 to 0.93 (m, 12H), 1.19 to1.35 (m, 16H); 1.48 to 1.61 (m, 2H); (m, 2H); 2.23 (t, J=7.5 Hz, 2H):4.86 (s, 2H): 7.25 to 7.40 (m, 5H): 7.72 (S, 1H).

¹³ C NMR (CDCl₃) 3.17, 6.90, 13.8, 22.5, 24.7, 28.9, 29.0, 29.1, 29.2,29.4, 31.7, 34.1, 56.4, 120.5, 127.6, 128.1, 130.1, 133.3, 138.0, 146.4,155.6, 173.8.

4-Dodecoyloxymethyl-5-hydroxy-3-phenyl-2(5H)-furanone

A mixture of 4-dodecoyloxymethyl-3-phenyl-2-triethylsiylfuran (256 mg,0.54 mmol), water (a few drops) and Rose Bengal on polymer beads (1.0 g)in tetrahydrofuran was exposed to singlet oxygen at 0 degrees for 3hours. The Rose Bengal was filtered off and the residue was concentratedto a pink oil which was purified by flash chromatography on silica using20% ethyl acetate/hexanes to give the title compound.

IR (CHCl₃) 3400 (v. broad), 1743 cm⁻¹.

¹ H NMR (CDCl₃): 0.88 (t, J=6.6 Hz, 3H); 1.05 to 1.45 (m, 16H); 1.50 to1.63 (m, 2H); 2.25 (t, J=7.6 Hz, 2H); 5.04 (S, 1H); 5.07 (S, 1H); 5.37to 5.50 (brs, 1H); 6.22 (S, 1H); 7.40 to 7.54 (m, 5H).

¹³ C NMR (CDCl₃): 14.1, 22.6, 24.6, 29.0, 29.2, 29.3, 29.4, 29.5, 31.8,33.8, 57.5, 96.5, 96.6, 128.1, 128.6, 129.1, 129.6, 131.7, 152.6, 170.5,173.6.

EXAMPLE 12 Ethyl-4-phenyl-3-furoate (Adapted from: Litta, D.; Saindane,M.; Ott, W. Tet. Lett. (1983) 24, 2473.)

A mixture of 4-phenyloxazole (500 mg, 3.45 mmol) and ethyl phenylpropiolate (630 mg, 3.62 mmol) were heated in a sealed tube for 16 hoursat 210 degrees with stirring. The residue was filtered through silicausing 5% ethyl ether/hexanes to give the titled oxazole, 664 mg of apale oil, which was used without further purification. The starting4-phenyloxazole was prepared according to Bredereck, H.; Gompper, R.Chem. Ber. (1945), 87, 700.

3-phenyl-4-furyl methanol (Compound 19)

LiAlH₄ (1.0 M solution in hexane 1.14 ml, 1.14 mmol) was added dropwiseto a solution of ethyl-4-phenyl-3-furoate, (246 mg, assumed 1.28 mmol)in tetrahydrofuran (20 ml) at 0 degrees under argon. The solution wasstirred and was allowed to warm to room temperature gradually over1/2hour. The mixture was quenched with saturated ammonium chloride andthe organics were extracted into ethyl ether, and washed with H₂ O.Evaporation of the dried (magnesium sulfate) extracts gave an oil, whichwas purified by flash chromatography on silica using 20% ethylacetate/hexanes. This was further purified by recrystallation(hexane/ethyl ether) to give the title compound as pale yellow crystals.

IR (CHCl₃): 3600 v. br., 3000 cm⁻¹.

¹ H NMR (CDCl₃): 1.90 (brs, 1H), 4.60 (brs, 2H), 7.22 to 7.60 (m, 7H).

¹³ C NMR (CDCl₃): 55.4, 124.1, 126.4, 127.4, 127.9, 128.9, 132.2, 140.4,142.3.

HRMS exact mass calculated for C₁₁ H₁₀ O₂ (M⁺) 174.0680, found 174.0696.

3-phenyl-4-furaldehyde (Compound 18)

A mixture of 3-phenyl-4-furylmethanol (Compound 19, 458 mg, 2.63 mmol),powdered 4A molecular sieves (500 mg), 4-methyl-morpholine-N-oxide (462mg, 3.95 mmol) and tetrapropylammonium perruthenate (46 mg, 0.13 mmol)in anhydrous dichloromethane (40 ml) were stirred at room temperaturefor 3 hours. Residue was filtered through silica and concentrated to abrown oil which was purified by flash chromatography on silica using 10%ethyl ether/hexanes to give the titled aldehyde.

IR (CHCl₃): 3020, 1690 cm⁻¹.

¹ H NMR (CDCl₃): 7.30 to 7.55 (m, 5H); 7.59 (d, J-1.6 HZ, 1H); 8.15 d,J=1.6 Hz, 1H); 9.94 (s, 1H).

¹³ C NMR (CDCl₃) 125.8, 126.1, 128.0, 128.6, 128.7, 130.0, 142.0, 152.6,185.2.

HRMS: exact mass Calculated for C₁₁ H₈ O₂ (M⁺) 172.0524 observed172.0520.

3(-1-acetoxytridecyl)-4-phenylfuran

Dodecylmagnesium bromide (a 1.0 M solution in THF; 2.11 ml, 2.11 mmol)was added to a solution of 4-phenyl-3-furaldehyde (303 mg, 1.76 mmol) inTHF at 0 degrees under argon and gradually allowed to warm to roomtemperature with stirring When all of the aldehyde was consumed aceticanhydride (719 mg, 7.04 mmol) was added and stirring was continued for 2hours more. The reaction was quenched with saturated ammonium chlorideand the organics were extracted into ethyl ether. The combined fractionswere washed with saturated sodium bicarbonate, water and brine, driedover magnesium sulfate and concentrated to a yellow oil which waspurified by flash chromatography on silica using 3% ethyl ether hexanesto give the title compound.

IR (CHCl₃): 3020, 1725 cm⁻¹.

¹ H NMR (CDCl₃): 0.88 (t, J=6.6 Hz, 3H); 1.10 to 1.40 (m, 20H); 1.53 to1.78 (m, 2H); 2.00 (s, 3H); 5.92 (t, J=6.8 Hz, 1H); 7.27 to 7.46 (m,7H).

¹³ C NMR (CDCl₃) 13.8, 20.9, 22.4, 25.1, 28.9, 29.1, 29.26, 29.36,29.41, 31.7, 34.4, 68.5, 124.6, 126.3, 127.4, 128.6, 128.8, 132.4,140.6, 141.5, 170.5.

HRMS: exact mass calculated for C₂₅ H₃₆ O₃ (M⁺) 384.2667, observed384.2672.

4-(-1-acetoxytridecyl)-5-hydroxy-3-phenyl-2(5H)-furanone3-(-1-acetoxytridecyl)-5-hydroxy-4-phenyl-2(5H)-furanone

A mixture of 3-(-1-acetoxytridecyl)-4-phenylfuran (506 mg, 1.32 mmol),water (a few drops) and Rose Bengal on polymer beads (1.6 g) in THF wasexposed to singlet oxygen at 0 degrees C. for 3 hours. The Rose Bengalwas filtered off and the residue was concentrated to a pink oil whichwas purified by flash chromatography on silica using 5 to 20% ethylacetate/hexanes to give the title furanones as a mixture of isomers. Theisomers were separated by HPLC chromatography on reverse phase Vydaccolumn using 15% water/acetonitrile.

3-(-1-acetoxytridecyl)-5-hydroxy-4-phenyl-2(5H)-furanone (retentiontime: 26.3 minutes).

IR (CDCl₃): 3020, 1760 cm⁻¹.

¹ H NMR (CDCl₃): 0.88 (t, J=6.7 Hz, 3H); 1.15 to 1.45 (m, 20H); 1.83 (s,3H); 1.77 to 1.92 (m, 1H); 1.92 to 2 07 (m, 1H); 5.59 (d, J=5.4 Hz 0.5H); 5.62 (d, J=5.4 Hz, 0.5 H); 6.31 (s, 1H); 7.40 to 7.54 m(5H).

¹³ C NMR (CDCl₃) 13.9, 20.3, 22., 25.4, 28.9, 29.16, 29.23, 29.34 29.41,29.45, 31.7, 32.6, 68.9, 97.6, 128.5, 128.7, 128.9, 130.2, 130.4, 157.9,169.6, 171.1.

LRMS m/z calculated for C₂₅ H₄₀ O₅ (M+NH₄)=434. Observed 434.

4-(-1-acetoxytridecyl)-5-hydroxy-3-phenyl-2(5H)-furanone (retention time28.0 minutes).

IR (CHCl₃): 3010, 1765 (V. br.)cm⁻¹.

¹ H NMR (CDCl₃): 0.88 (t, J=6.5 Hz, 3H); 1.12 to 1.40 (m, 20H); 1.81 (s,3H); 170 to 185 (m, 1H); 1.85 to 2.00 (m, 1H); 5.62 (d, J=5.1 Hz, 0.5H); 5.65 (d, J=5.0 Hz, 0.5 H); 6.17 (s, 1H); 7.33 to 7.50 (m, 5H).

¹³ C NMR (CDCl₃): 13.8, 20.1, 22.4, 25.3, 28.8, 29.1, 29.2, 29.3, 29.4,31.7, 33.0, 70.3, 97.2, 128.6, 128.9, 129.4, 131.1, 156.8, 170.7, 171.3.

LRMS m/Z calculated for C₂₅ H₄₀ O₅ (M+NH₄)-434, observed 434.

2-Methyl-4-phenyl-3-furaldehyde (Compound 16)

n-Butyllithium (a 1.6 m solution in hexane, 2.43 ml, 3.89 mmol) wasadded to a solution of trimethylethylenediamine (397 mg, 3.89 mmol) intetrahydrofuran (25 ml) at 0 degrees under argon. After 20 minutes thesolution was cooled to -78 degrees and 3-phenyl-4-furaldehyde (Compound18, 608 mg, 3.35 mmol) was added. This mixture was allowed to graduallywarm to -20 degrees and stirred for 11/2 hours, then recooled to -78degrees before n-butyllithium (a 1.6 M solution in hexane, 2.43 ml, 3.89mmol) was added dropwise. The stirring mixture was again graduallywarmed to -20 degrees and stirred for 2 hours before iodomethane (2.56 g17.67 mmol) was added. After o stirring for 18 hours at -20 degrees thereaction was quenched with ice-cold 10% (v/v) hydrochloric acid and theorganics were extracted into ethyl ether. The combined fractions werewashed with saturated sodium bicarbonate, H₂ O and brine. Evaporation ofthe dried (magnesium sulfate) extracts gave an oil which was purified byflash chromatography on silica using 20% ethyl ether/hexanes to give thetitle aldehyde.

IR (CHCL₃) 3600, 1690 cm⁻¹.

¹ H NMR (CDCl₃): 2.65 (s, 3H); 7.30 to 7.50 (m, 6H); 1.02 (s, 1H).

¹³ C NMR (CDCl₃) 13.4, 119.8, 127.2, 128.0, 128.7, 129.0, 130.6, 138.3,162.3, 186.7.

HRMS: exact mass calculated for C₁₂ H₁₀ O₂ (M⁺) 186.0680, found186.0689.

2-Methyl-4-phenyl-3-furylmethanol (Compound 17)

LiAlH₄ (1.0 M solution in hexane, 0.12 ml, 0.12 mmol) was added dropwiseto a solution of 2-methyl-4-phenyl-3-furaldehyde (Compound 58, 45 mg,0.24 mmol) in tetrahydrofuran (3 ml) at 0 degrees under argon. After 10minutes the reaction was quenched with saturated ammonium chloride andthe organics were extracted into ethyl ether. The combined fractionswere washed with H₂ O and brine and the dried (magnesium sulfate)extracts were concentrated to a yellow oil which was carried on withoutfurther purification.

IR (CHCl₃) 3620, 3450 (v. broad), 3005 cm⁻¹.

¹ H NMR (CDCl₃): 2.38 (S, 3H); 4.56 (s, 2H); 7.25 to 7.60 (m, 6H);

¹³ C NMR (CDCl₃) 11.5, 54.8, 117.9, 127.2, 127.5, 128.1, 128.9, 132.7,137.4, 151.9.

HRMS exact mass calculated for C₁₂ H₁₂ O₂ (M+) 188.0837, found 188.0850.

3-Dodecoyloxymethyl-2-methyl-4-phenylfuran

To a stirred solution of 2-methyl-4-phenyl-3-furylmethanol (Compound 17,48 mg, 0.26 mmol) and triethylamine (39 mg. 0.38 mmol) intetrahydrofuran (3 ml) at 0 degrees under argon was added lauroylchloride (73 mg. 0.33 mmol). This solution was warmed gradually to roomtemperature and stirred for 41/2hours. The organics were extracted intoethyl ether and washed with a 5% aqueous sodium bicarbonate solution, H₂O and brine. Evaporation of the dried (magnesium sulfate) extracts gavean oil which was purified by flash chromatography on silica using 3%ether/hexanes to give the title compound.

IR (CHCl₃): 3010, 1725 cm⁻¹.

1H NMR (CDCl₃): 0.86 (t, J=6.7 Hz, 3H); 1.20 to 1.32 (m, 16H); 1.50 to1.64 (m, 2H); 2.23 to 2.32 (m, 2H); 2.36 (s, 3H); 4.97 (s, 2H); 7.29 to7.42 (m, 6H).

¹³ C NMR (CDCl₃): 11.7, 13.9, 22.5, 24.7, 28.9, 29.06, 29.12, 29.3,29.4, 31.7, 34.2, 56.5, 113.7, 127.3, 127.9, 128.1, 128.8, 132.5, 137.6,153.3, 174.1.

4-Dodecoyloxymethyl-5-hydroxy-5-methyl-3-phenyl-2-furanone

A mixture of 3-dodecoyloxymethyl-2-methyl-4-phenylfuran (40 mg, 0.11mmol), water (a few drops) and Rose Bengal on polymer beads (240 mg) intetrahydrofuran (40 ml) was exposed to singlet oxygen at 0 degrees for 3hours. The Rose Bengal was filtered off and the residue was concentratedto a pink oil which was purified by flash chromatography on silica using15% ethyl acetate/hexanes. The furanone was further purified by HPLCchromatography on a normal phase partisil 10 column using 15% ethylacetate/hexanes to give the title compound.

IR (CHCl₃): 3020, 1765, 1740 cm⁻¹.

¹ H NMR (CDCl₃): 0.85 (t, J=6.7 Hz, 3H): 1.10 to 1.21 (m, 16H); 1.35 to1.49 (m, 2H); 1.77 (s, 3H); 2.11 (t, J=7.6 Hz, 2H); 3.70 to 3.90 (brs,1H); 5.02 (s, 2H); 7.37 to 7.50 (m, 5H).

¹³ C NMR (CDCl₃): 13.9, 22.5, 24.0, 24.4, 28.9, 29.0, 29.1, 29.2, 29.4,31.7, 33.6, 57.2, 104.4 128.4, 128.7, 129.4, 129.8, 131.4, 154.4, 169.0,173.9.

HRMS: exact mass calculated for C₂₄ H₃₅ O₅ (MH⁺) 403.2484, found403.2497.

5-Methyl-2-triethylsilyl-4-furylmethanol

LiAlH₄ (1.0 M solution in hexane, 0.51 ml, 0.51 mmol) was added dropwiseto a solution of 5-methyl-2-triethylsilyl-4-furaldehyde (230 mg, 1.03mmol) in tetrahydrofuran (15 ml) at 0 degrees under argon. The stirringsolution was allowed to warm to room temperature gradually over 1/2hour. The reaction was quenched with I0% aqueous HCl and the organicswere extracted into ethyl ether. The combined fractions were washed withH₂ O and brine. Evaporation of the dried (magnesium sulfate) extractsgave an oil which was purified by filtration through silica using 10%ethyl ether/hexanes to give the title compound.

IR (CHCl₃): 3610 (sharp), 3440 (broad), 2940 cm⁻¹.

¹ H NMR (CDCl₃): 0.71 (q, J=7.7 Hz, 6H); 0.96 (t, J=7.7 Hz, 9H); 2.25(s, 3H); 2.40 (brs, 1H); 4.38 (s, 2H); 6.59 (s, 1H).

¹³ C NMR (CDCl₃): 2.9, 11.5, 56.2, 118.9, 122.3, 153.7, 156 0.

4-Dodecoyloxymethyl-5-methyl-2-triethylsilylfuran

To a stirred solution of 5-methyl-2-triethylsilyl-4-furylmethanol (208mg. 0.92 mmol) and triethylamine (121 mg, 1.20 mmol) in tetrahydrofuran(10 ml) at 0 degrees under argon was added lauroyl chloride 302 mg, 1.38mmol). This solution was allowed to warm gradually to room temperatureand quenched with a 10% aqueous HCl solution. The organics wereextracted into hexanes and the combined fractions were washed with asaturated aqueous solution of sodium bicarbonate, H₂ O and brineEvaporation of the dried (magnesium sulfate) extracts gave an oil whichwas purified by filtration through silica using 2% ethyl ether/hexanesto give the title compound.

IR (CHCl₃): 1725 cm⁻¹.

¹ H NMR (CDCl₃): 0.75 (q, J=7.7 Hz, 6H); 0.88 (t, J=6.7 Hz, 3H), 0.98(t, J=7.7 Hz, 9H); 1.20 to 1.35 (m, 16H); 1.56 to 1.68 (m, 2H); 2.30 (t,J=7.5 Hz, 2H); 2.3I (s, 3H); 4.91 (s, 2H); 6.57 (s, 1H).

¹³ C NMR (CDCl₃): 2.9, 7.0, 11.7, 13.8, 22.6, 24.8, 28.9, 155.3, 156.3,174.2.

4-Dodecoyloxymethyl-5-hydroxy-5-methyl-2-furanone

A mixture of 4-dodecoyloxymethyl-5-methyl-2-triethylsilylfuran (180 mg.0.44 mmol), water (a few drops) and Rose Bengal on polymer beads (360mg) in tetrahydrofuran (70 ml) was exposed to singlet oxygen at 0degrees until no starting material was visible (via TLC). The RoseBengal was filtered off and the residue was concentrated to a pink oilwhich was purified by flash chromatography on silica using 30% ethylacetate/hexanes to give the titled furanone.

IR (CHCl₃): 3400 (v. broad), 1750 (strong) cm⁻¹.

¹ H NMR (CDCl₃): 0.88 (t, J=6.7 Hz 3H); 1.20 to 1.37 (m, 16H); 1.59 to1.70 (m, 2H); 1.72 (s, 3H); 2.40 (t, J=7.6 Hz, 2H); 3.20 to 4.40 (v.brs, 1H); 4.93 (s, 2H); 5.94 (s, 1H).

¹³ C NMR (CDCl₃): 13.8, 22.4, 23.7, 24.5, 28.8, 28.9, 29.0, 29.2, 29.3,31.6, 33.7, 58.4, 105.9, 117.0, 166.2, 170.3, 173.7.

EXAMPLE 13 2-Trimethylsilyl-3-furaldehyde

N,N',N'-Triemthylethylenediamine (9.72 ml, 76 mmol) was added to asolution of n-butyl lithium (a 2.5M solution in hexane; 30.5 ml, 76mmol) in tetrahydrofuran (200 ml) as -78° under argon. After 15 minutes,3-furaldehyde 6.3 ml, 72.8 mmol) was added, which was followed after 25minutes by n-butyl-lithium (32ml, 80 mmol). Even better results (moreselectively) are obtained when methyl lithium is used instead of butyllithium. After another 4 hours, chlorotrimethylsilane (11 ml, 87 mmol)was added. Stirring was continued for 14 hours, while the cooling bathwas allowed to warm to room temperature. The mixture was quenched withice-cold hydrochloric acid and was extracted with ethyl ether.Evaporation of the dried (magnesium sulfate) extracts gave an oil, whichwas distilled to give the title aldehyde, b.p. 40-1°/0.1 torr.

¹ H NMR (CDCl₃): 2.89 (s, 3H), 6.97 (d, 1H, J=1.9 Hz), 7.59 (d, 1H,J=1.9 Hz) and 10.23 (s, 1H).

¹³ CNMR (CDCl₃): -1.89, 107.7, 137.1, 147.3, 171.1 and 185.7.

Substituting chlorotrimethylsilane with chlorotriethylsilane gave2-triethylsilyl-3-furaldehyde (Compound 15).

4-(1-Acetoxynonyl)-2-trimethylsilyfuran

A solution of 2-trimethylsilyl-3-furaldehyde (1.0 g, 5.90 mmol) intetrahydrofuran (2ml) was added to a solution of octyl magnesium bromide(11.9 mmol; prepared from 2.30 g 1-bromo octane and 286 mg magnesiumturnings) at 0°. After all the aldehyde was consumed in the reaction, asmonitored by thin layer chromatography (tlc) acetic anhydride was addedand stirring was continued for overnight. Thereafter, the mixture wasquenched with dilute hydrochloric acid and was extracted with ethylether. Evaporation of the dried (magnesium sulfate) extracts gave anoil, which was purified by a silica column using 5% ethyl ether/hexaneto give the title furan.

¹ HNMR (CDCl₃): 0.34 (s, 9H), 0.89 (t, 3H, J=7.2 Hz), 1.27 (br s, 12H),1.75 (2m, 2H), 2.05 (s, 3H), 5.89 (t, 1H, J =7.3 Hz), 6.45 (d, 1H, J=1.6Hz) and 7.28 (br s, 1H).

LRMS (m/e, % abundance) 324 (M⁺, 7), 282(43), 281(88), 267(13), 266(31),265(15), 169(26), 153(47), 117(100), 75(38) and 73(78).

3-(1-Acetoxynonyl)-5-hydroxy-2(5H)-furanone

A mixture of 3-(1-acetoxynonyl)-2-trimethylsilyfuran (1.40 g, 4.32mmol), water (5 drops) and Rose Bengal (3 mg) in tetrahydrofuran (20 ml)was exposed to singlet oxygen at 0° for 6 hours. The residue, aftersolvent removal, was purified by a silica column using 50% ethylether/hexane to give the title furanone.

¹ HNMR (CDCl₃): 0.91 (t, 3H, J=7.0 Hz), 1.29 (br s, 12H), 1.85 (m, 2H),2.15 (s, 3H), 4.20 (br, 1H), 5.60 (m, 1H), 6.14 (br s, 1H) and 7.00 (brs, 1H).

¹³ CNMR (CDCl₃): 13.9, 20.8, 22.5, 24.8, 29.0, 29.2, 31.7, 32.6, 32.8,68.4, 68.7, 96.9, 97.2, 136.7, 145.3, 169.7, 170.6 and 170.8.

HRMS exact mass calculated for C₁₅ H₂₅ O₅ (M+H)⁺ 295.1702, found285.1709.

3-(1-Acetoxynonyl)-2(5H)-furanone (Compound 70)

Sodium borohydride (29.3 mg, 0.76 mmol) was added to a solution of3-(1-acetoxynonyl)-5-hydroxy-2(5H)-furanone (220 mg, 0.78 mmol) inmethanol (1 ml) and tetrahydrofuran (5 ml). Stirring was continued for14 hours at room temperature and most of the solvent was evaporated. Theresidue was acidified with ice-cold dilute hydrochloric acid and wasextracted with ethyl acetate. Evaporation of the dried (magnesiumsulfate) extracts gave an oil, which was purified by preparative silicaplates (developed with 60% ethyl ether/hexane) to give the titlefuranone.

¹ HNMR (CDCl₃): 0.88 (t, 3H, J=6.5 Hz), 1.25 (m, 12H), 1.85 (m, 2H),2.11 (s, 3H), 4.82 (m, 2H), 5.61 (t, 1H, J=6.3 Hz) and 7.29 (t, 1H,J=1.5 Hz).

¹³ CNMR (CDCl₃): 14.0, 20.9, 22.6, 24.9, 28.9, 29.1, 29.3, 31.7, 32.6,68.9, 70.1, 133.6, 146.1, 169.9 and 171.6.

HRMS exact mass calculated for C₁₅ H₂₅ O₄ (M+H)⁺ 269.1753, found269.1735.

3-(1-Hydroxytridecyl)-2-trimethylsilyfuran

A solution of dodecylmagnesium bromide (a 1M solution intetrahydrofuran; 14.3 ml; 14.3 mmol) was added to a solution of2-trimethylsilyl-3-furaldehyde (1.20 g, 7.1 mmol) in tetrahydrofuran (30ml) at 0°. After all the aldehyde has reacted, as shown by tlc, themixture was quenched with dilute hydrochloric acid and was extractedwith ethyl ether. Evaporation fop the dried (magnesium sulfate) extractsgave an oil, which was purified by a silica column using 5% ethylether/hexane to give the title furan.

¹ HNMR (CDCl₃): 0.34 (s, 9H), 0.91 (t, 3H, J=6.9 Hz), 1.28 (br s, 20H),1.75 (m, 2H), 4.75 (m, 1H), 6.48 (d, 1H, J=1.7 Hz) and 7.60 (d, 1H,J=1.7Hz).

HRMS exact mass calculated for C₂₀ H₃₈ SiO₂ (M⁺) 338.2641, found338.2643.

3-(1-Hydroxytridecyl)-5-hydroxy-2(5H)-furanone

A mixture of 3-(1-hydroxytridecyl)-2-trimethylsilyfuran (1.17 g, 3.46mmol), water (5 drops) and Rose Bengal (5 mg) in tetrahydrofuran (20 ml)was exposed to singlet oxygen at 0° for 6 hours. The residue, aftersolvent removal, was purified by a silica column using 60% ethylether/hexane to give the title furanone.

¹ HNMR (CDCl₃): 0.90 (t, 3H, J=7.0 Hz), 1.28 (br s, 20H), 1.75 (m, 2H),2.85 (br, 1H), 4.50 (br t, 1H), 4.70 (br, 1H), 6.15 (br s, 1H) and 7.06(br s, 1H).

¹³ CNMR (CDCl₃): 14.0, 22.6, 25.3, 29.3, 29.4, 29.6, 29.7, 31.9, 35.0,66.2, 66.5, 97.5, 97.6, 139.8, 145.2, 145.4 and 171.4.

HRMS exact mass calculated for C₁₇ H₃₁ O₄ (M+H)⁺ 299.2222, found299.2224.

3-(1-Hydroxytridecyl)-2(5H)-furanone (Compound 71)

Sodium borohydride (31.3 mg, 0.83 mmol) was added to a solution of3-(1-hydroxytridecyl)-5-hydroxy-2(5H)-furanone (246.9 mg, 0.83 mmol) inmethanol (1 ml) and tetrahydrofuran (5 ml). When all the furanone wasconsumed, most of the solvent was evaporated. The residue was acidifiedwith dilute hydrochloric acid and was extracted with ethyl acetate.Evaporation of the dried (magnesium sulfate) extracts gave an oil, whichwas purified by preparative silica plates (developed with 60% ethylether/hexane) to give the title furanone.

¹ HNMR (CDCl₃): 0.88 (t, 3H, J=6.2 Hz), 1.25 (m, 20H), 1.70 (m, 2H),2.55 (br s, 1H), 4.51 (t, 1H, J=6.2Hz), 4.84 (m, 2H), and 7.30 (t, 1H,J=1.5Hz).

¹³ CNMR (CDCl₃): 13.9, 22.5, 25.1, 29.2, 29.3, 29.4, 29.5, 31.8, 35.3,66.8, 70.4, 136.5, 145.1 and 173.2.

HRMS exact mass calculated for C₁₇ H₃₁ O₃ (M+H)⁺ 283.2273, found283.2254.

3(1-Acetoxytridecyl)-2-trimethylsilyfuran

Dodecylmagnesium bromide (a 1.0 M solution in tetrahydrofuran; 14.3 ml;14.3 mmol) was added to a solution of 2-trimethylsilyl-3-furaldehyde(1.20 g, 7.1 mmol) in tetrahydrofuran (20 ml). When all the aldehyde wasconsumed, as monitored by tlc, acetic anhydride (2.02 ml, 21.4 mmol) wasadded. Stirring was continued at room temperature for 14 hours. Themixture was quenched with water and was extracted with ethyl ether.Evaporation of the dried (magnesium sulfate) extracts gave an oil, whichwas purified by a silica column using 2% ethyl ether/hexane to give thetitled furan.

¹ HNMR (CDCl₃): 0.34 (s, 9H), 0.89 (t, 3H, J=6.9 Hz), 1.26 (br s, 20H),1.75 (m, 2H), 2.04 (s, 3H), 5.8 (t, 1H, J=7.1Hz), 6.43 (br s, 1H) and7.58 (br s, 1H).

HRMS exact mass calculated for C₂₂ H₄₀ O₃ Si(M⁺) 380,2747, found380.2752.

3(1-Acetoxytridecyl)-2(5H)-furanone

A mixture of 3-(1-acetoxytridecyl)-2-trimethylsilyfuran (1.25 g, 3.29mmol), water (5 drops) and Rose Bengal (5 mg) in tetrahydrofuran (10 ml)was exposed to singlet oxygen at 0° for 6 hours. The residue, aftersolvent removal, was purified by a silica column using 50% ethylether/hexane to give the title furanone.

¹ HNMR (CDCl₃): 0.93 (t, 3H, J=6.9 Hz), 1.29 (br s, 20H), 1.85 (s, 3H),4.20 (br, 1H), 5.60 (br t, 1H), 6.15 (br s, 1H) and 7.02 (br s, 1H).

¹³ CNMR (CDCl₃): 14.0, 20.8, 22.6, 24.9, 28.8, 28.9, 29.0, 29.1, 29.3,29.5, 29.6, 31.5, 31.8, 32.7, 32.8, 68.5, 68.7, 68.8 96.9, 97.0, 97.2,136.8, 145.2, 145.3, 169.7, 170.6 and 170.7.

3(1-Acetoxytridecyl)-2(5H)-furanone (Compound 72)

Sodium borohydride (251 mg, 0.74 mmol) was added to a solution of3-(1-acetoxytridecyl)-5-hydroxy-2(5H)-furanone (251 mg, 0.74 mmol) inmethanol (1 ml) and tetrahydrofuran (5 ml). at room temperature. Whenall the furanone were consumed, as monitored by tlc, the solution wasevaporated to dryness. The residue was acidified with dilutehydrochloric acid and was extracted with ethyl acetate. Evaporation ofthe dried (magnesium sulfate) extracts gave an oil, which was purifiedby preparative silica plates (developed with 60% ethyl ether/hexane) togive the title furanone.

¹ HNMR (CDCl₃): 0.88 (t, 3H, J-6.5 Hz), 1.25 (m, 20H), 1.85 (m, 2H),2.10 (s, 3H), 4.80 (m, 2H), 5.60 (t,1H, J=6.0 Hz) and 7.29 (t, 1H,J=1.6Hz).

¹³ CNMR (CDCl₃): 13.7, 20.6, 22.3, 24.7, 28.9, 29.0, 29.1, 29.2, 29.3,31.6, 32.4, 68.8, 70.0, 133.7, 146.4, 170.2 and 171.9.

HRMS exact mass calculated for C₁₉ H₃₃ O₄ (M+H)⁺ 325.2379, found325.2376.

3-(1-phenylcarbamoyloxytridecyl)-2(5H)-furanone

3-(-1-Hydroxytridecyl)-2-trimethylsilyfuran is reacted with phenylisocyanate and copper (2) chloride in dimethylformamide to give3-(1-phenylcarbamoyloxytridecyl)-2-trimethylsilyfuran. Oxidizing thelatter intermediate with singlet oxygen and thereafter reduction withsodium borohydride gives3-(1-phenylcarbamoyloxytridecyl)-2(5H)-furanone. Substituting phenylisocyanate with diethyl chlorophosphate, gives3-(1-diethylphosphonooxytridecyl)-2(5H)-furanone. Substituting phenylisocyanate with ethyl chloroformate, gives3-(1-ethoxycarbonyloxytridecyl)-2(5H)-furanone. Substituting phenylisocyanate with methoxyethyl chloromethyl ether, gives3-[1-(2-methoxy)ethoxymethoxy]tridecyl-2(5H)-furanone.

3-(1-acetamidotridecyl)-2(5H)-furanone

Reaction 3-(1-hydroxytridecyl)-2-trimethylsilyfuran withdiphenylphospohoryl azide and diethyl azidocarboxylate gives3-(1-azidotridecyl)-2-triethylsilyfuran. Reducing this intermediate withlithium aluminum hydride followed by acetylation with acetic anhydridegives 3-(1-acetamido tridecyl)-2-trimethylsilyfuran. Singlet oxygenoxidation of this amide, followed by reduction with sodium borohydridegives 3-(1-acetamidotridecyl)-2(5H)-furanone.

3-(1-methanesulfonamidotridecyl)-2(5H)-furanone

Reducing 3-(1-azidotridecyl)-2-trimethylsilyfuran with lithium aluminumhydride, as in Example 8, followed by reacting the intermediate withmethanesulfonyl chloride, gives3-(1-methanesulfonamidotridecyl)-2-trimethylsilyfuran. Oxidizing thissulfonamide followed by reduction with sodium borohydride gives3-(1-methanesulfonamidotridecyl)-2(5H)-furanone.

ACTIVITY DATA

In the above-described phospholipase A₂ (PLA₂) and calcium⁺ channelmobilization assays certain examplary compounds made from the syntheticintermediate compounds of the present invention had the followingactivities.

                  TABLE 1                                                         ______________________________________                                        Phospholipase A.sub.2 Assay.                                                  Compound name or number                                                                         IC.sub.50 (micromolar)                                      ______________________________________                                        manolide*         0.03                                                        20                >1                                                          21                0.03                                                        22                0.05                                                        23                0.04                                                        24                0.34                                                        25                0.26                                                        26                0.13                                                        27                0.04                                                        28                0.04                                                        29                0.07                                                        30                0.06                                                        31                0.05                                                        32                0.48                                                        40                0.28                                                        41                0.04                                                        42                0.03                                                        43                0.03                                                        44                0.09                                                        45                0.05                                                        46                0.02                                                        47                0.06                                                        50                0.5                                                         51                0.09                                                        60                0.06                                                        61                >1                                                          62                0.24                                                        ______________________________________                                         *Data for monoalide are provided for comparison.                         

                  TABLE 2                                                         ______________________________________                                        Calcium Channel Inhibition Assay.                                                           IC.sub.50 (umolar)                                                                         IC.sub.50 (umolar)                                 Compound number                                                                             (TRH regulated)                                                                            (KCl regulated)                                    ______________________________________                                        70            4.9          3.4                                                71            2            1.1                                                72            16.9         0.88                                               manoalide     1.0          1.0                                                ______________________________________                                    

What is claimed is:
 1. A compound of the formula ##STR19## where Z isCH═O,R₆ is phenyl or lower alkyl of 1 to 6 carbons, and n is 1 or 2 andwhere the R₆ groups are attached to the 2 and 4 positions or both, ofthe furane ring.
 2. A compound of claim 1 which is2-methyl-4-phenyl-3-furaldehyde or 3-phenyl-4-furaldehyde.
 3. A compoundof claim 1 where R₆ is phenyl.
 4. A compound of claim 1 where R₆ loweralkyl.
 5. A compound of claim 1 where n is
 1. 6. A compound of claim 1where n is
 2. 7. A compound of the formula ##STR20## where Z is --CH₂OH,R₆ is phenyl and R₅ is H, phenyl or lower alkyl, n is zero or 1, andwhere the R₆ and R₅ groups are attached to 2 or 4 positions of thefuranone ring.